Name: partial bile duct ligation in the mouse: a controlled model of localized obstructive cholestasis
Uploaded: 2018-03-28T13:00:00.000+00:00
Duration: 4 min 38 s
Description: Watch this Scientific Journal Video about Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis at JoVE.com

Dr. Khan reconhece apoio de concessão da K12HD052892 NIH/FORMULADORES, a Alpha-1 Foundation, Fundação Hillman e centro de pesquisa do fígado de Pittsburgh. Dr. Michalopoulos reconhece apoio de concessão do NIH/NIDDK P01DK096990. Agradecemos a assistência técnica excelente e generosa de Anne Orr. Nós também estamos gratos ao Dr. David A. Geller para fornecer acesso ao laboratório de microcirurgia do transplante/roedor.

Todos os procedimentos foram realizados em conformidade com as diretrizes éticas do Comité de uso da Universidade de Pittsburgh e institucional Cuidado Animal.
1. básicas técnicas e procedimentos comuns
<ol><li>Autoclave todo equipamento microcirúrgico antes do uso.</li>
	<li>Para evitar matar o rato pela anestesia, verificar cuidadosamente seu padrão de respiração.</li>
	<li>Órgãos de toque e intestinos o mínimo possível para evitar danificar os órgãos e causando sangramento. Pressione pontos de sangramento com cotonetes de algodão molhado ou esponjas de gaze.</li>
	<li>Use cotonetes de algodão molhado para manipulação suave dos órgãos. Esponjas de gaze molhada, não-tecidos são utilizadas em dois tamanhos, 3.5 × 3,5 cm e 6,0 × 6,0 cm. usam o menorzinho para retrair o fígado inteiro. Use o maior para embrulhar os intestinos pequenos e grandes.</li>
</ol>2. pré-operatória preparação
<ol><li>Use Camundongos c57/b6 do sexo masculino, 8-12 semanas de idade (quando o peso do corpo é aproximadamente 20-35 g) para ligadura parcial de ducto biliar.</li>
	<li>Permitir que os ratos livre acesso à água e comida até a indução da anestesia.</li>
</ol>3. parcial biliar ligadura operação
<ol><li>Anestesia o mouse, colocando o animal em uma câmara de indução com uma mistura de 1,5-2,0% de isoflurano e 1 L/min de oxigênio. Monitore o animal cuidadosamente observando-se a taxa de respiração. Quando a taxa de respiração do animal é uma respiração por segundo, o rato é bem anestesiado. Desde que o reflexo de retirada do membro dianteiro desaparece mais rapidamente, aperte o pé do membro posterior também para confirmar a ausência completa do reflexo de retirada. Os olhos devem ser lubrificados com um agente lubrificante oftálmico para evitar úlceras da córnea. Nota a primeira dose de analgésico pode ser dado pré-operatório para prevenir a estimulação dos receptores de dor.</li>
	<li>Raspar a parede abdominal com máquina de cortar cabelo e coloque o mouse em cima da mesa cirúrgica sob o microscópio cirúrgico. Corrigi todos os membros para a mesa com a fita. Use a inalação de isoflurano para manter o rato sob anestesia geral.<ol>
<li>Ajustar o vaporizador de isoflurano e usar isoflurano 2.0-3.0% para indução.</li>
	</ol>
</li>
	<li>Usando cotonetes estéreis, desinfectar a parede abdominal primeiro com 0,3-0,5 mL de iodo-povidona aplicado topicamente, seguido por 70% de etanol. Animal deve ser coberto com um pano estéril.</li>
	<li>Fazer uma longa abdominal incisão do xifoide até o púbis, usando a tesoura e pinça Adson. Depois de fazer a incisão abdominal, reduzir isoflurano 0.8-1.0% para manutenção.</li>
	<li>Expor na cavidade abdominal por meio de um Microafastador. Segure o xifoide com pinça mosquito e retrair-se em direção a cabeça do rato. Fixar a pinça mosquito com argila macia.</li>
	<li>Instilar 1 a 2 mL de aquecida (37 ° C) esterilizado fosfato salino (PBS) na cavidade abdominal para evitar ferir os órgãos abdominais. Segure o intestino delgado com compressas de algodão molhado e retrair-os suavemente em direção a cabeça do rato. Corte os ligamentos entre o intestino delgado e o retroperitônio para evitar ferir o intestino delgado (figura 1A).</li>
	<li>Enrole os intestinos pequenos e grandes com uma gaze molhada, não-tecidos. Coloque-os no lado caudal da cavidade abdominal. Intestinos, envolvidos em gaze estéril podem ser colocados no Campo drapeado estéril para evitar contaminação.</li>
	<li>Gentilmente retrai o fígado inteiro em direção a xifoide usando um pequeno molhado não-tecido de gaze para expor o Hilo hepático e ligamento hepato-duodenal (figura 1B).</li>
	<li>Verificação para confirmar a anatomia do hilo hepático. O ducto biliar comum está localizado no lado ventral da veia portal. Confirme os locais do direito e o ducto biliar hepático esquerdo, que drenam para a confluência biliar principal no hilo hepático.</li>
	<li>Identificar o ducto biliar hepático esquerdo que drena o lobo esquerdo e cercá-lo com uma sutura de nylon 10-0 usando o lado sem corte de uma agulha de sutura (Figura 2A). Evite ferir a superfície hepática, artéria hepática e veia porta.</li>
	<li>Ligate do ducto biliar esquerdo com nylon 10-0. (Figura 2B).</li>
	<li>Coloque os intestinos pequenos e grandes na mesma posição que antes da operação, usando cotonetes de algodão molhado.</li>
	<li>Confirmar que não há nenhuma torção intestinal e hemorragia abdominal e, em seguida, feche o músculo e a pele em duas camadas com vicryl 4-0. Sutura trançada (Vicryl) foi usada para fechamento da pele, mas é preferível monofilamento para reduzir a probabilidade de infecção. Nota: Feche a fáscia por sutura contínua do xifoide ao púbis e fechar a pele por sutura contínua do púbis ao xifoide.</li>
	<li>Pare de anestesia depois de fechar a incisão.</li>
</ol>4. acompanhamento e tratamento pós-operatório
<ol><li>Só após a cirurgia, beliscar a pele dorsal do mouse e injetar Buprenex (0,1 mg/kg) e cefazolina (100 mg/kg) por via subcutânea, seguido por Buprenex injeção cada 12 h por 3 dias e cefazolina cada 24 h por 3 dias respectivamente11,12 ,13. Nota a primeira dose de analgésico pode ser dado pré-operatório para prevenir a estimulação dos receptores de dor. Cefazolina e outros antibióticos de peri-operatório são necessários apenas para animais imunitário suprimido, como aqueles usados em estudos de transplante. Nota: Se a cirurgia é realizada com êxito, o mouse geralmente se recupera dentro de 30 min. actividade dos ratos será quase o mesmo que a condição pré-operatória.</li>
	<li>Verifique os ratos diariamente por sinais de aflição.<ol>
<li>Sacrifica os ratos pelo deslocamento cervical sob anestesia geral para adquirir fígados e outras amostras de tecido em pontos de tempo definido (isto é, 7, 14, 21 dias) depois de pBDL.</li>
	</ol>
</li>
</ol>

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Embora cBDL é a mais comum técnica experimental para colestase obstrutiva, pode apresentar vários desafios em roedores. Dependendo do número de dias pós-operatórios necessários para alcançar um ponto de extremidade, os animais podem experimentar significativa morbidade e mortalidade que o tempo avança. O grau de lesão tecidual e necrose biliar é ainda agravado quando se trabalha com alguns modelos de rato transgénico de doença hepática, que demonstram o parênquima hepática anormal e função na linha de b...

Modelos cirúrgicos da lesão hepática aguda e reparação, tais como hepatectomy parcial ou ligadura do ducto biliar comum (cBDL), têm sido utilizados há décadas em roedores para estudar a regeneração hepática e Patobiológico1,2. Em cBDL, é ligado o ducto biliar comum (que drena todas bile produzida no fígado), resultando em colestase obstrutiva, inflamação e fibrose nas primeiras 2-3 semanas após a cirurgia, com eventual progressão para cirrose3. Proliferação do ducto biliar, transdiferenciação celular e indução de células progenitoras de fígado residente são também características da cBDL4,5. Embora cBDL elucida mecanismos específicos de cholangiopathy obstrutiva, que são bem caracterizados com resultados reprodutíveis em ratos do selvagem-tipo e nessas cepas com fígados normal6,7,8, o procedimento pode ser tecnicamente exigente em alguns modelos de rato transgénico, doenças do fígado, que exigem mais animais do que o previsto devido à maior morbidade e mortalidade de obstrução biliar, ao longo do tempo. Esta técnica é também benéfica para estudar doença de ratos transgénicos com subjacentes fígado, que não pode tolerar senão o stress das experiências de curso prolongado após cBDL.
pBDL pode fornecer uma alternativa razoável para ajudar a superar alguns desses desafios. Estudos de pBDL inicial em ratos do selvagem-tipo visa distinguir localmente atuante e sistêmicos de mediadores da inflamação9. De pBDL, confluência biliar principal de direita e esquerdas hepáticas biliares acima o ducto biliar comum com cuidado é visualizada no hilo, e apenas esquerdo hepático ducto biliar é ligado para gerar uma colestase obstrutiva localizada. pBDL oferece várias vantagens para cBDL. De pBDL, unligated lóbulo direito serve como um controle interno forma idêntica correspondente para o lobo esquerdo ligado, sujeitado para os mesmos efeitos sistêmicos, tais como o estado nutricional ou fatores de circulação. Embora mediadores pró-inflamatórios sistêmicos estavam presentes, Osawa et al observou menos fibrose e necrose dos lóbulos unligated, mas aumento de células inflamatórias e expressão de crescimento fator-β transformador do lóbulo ligados9.
Mais recentemente, foi redefinido para estudar efeitos parenquimatosos hepáticas da bile retida10pBDL. Usando o mesmo animal para controle interno (unligated "sham") e grupos experimentais, pBDL metades efetivamente o número de animais necessários por experiência, que por sua vez, é mais rentável. Os ratos toleram os efeitos de pBDL muito melhor, para que o tempo ideal de curso experimentar (≥2 semanas) podem ser alcançadas no lóbulo ligado. Mais importante ainda, pBDL pode distinguir efeitos directos de colestase da colestase obstrutiva e retidos componentes da bile no lóbulo ligado, em comparação com o lobo de unligated controle. Em geral, pBDL é um método atrativo para estudar efeitos específicos do lóbulo da colestase localizada no fígado.

<table><tbody><tr><td>Microscope-Leica Wild M650, 6&amp;ndash;40&amp;times; magnification</td><td>Leica Microsystems</td><td>n/a</td><td></td></tr><tr><td>Tec 3 isoflurane funnel fill vaporizer</td><td>General Anesthetic Services</td><td>n/a</td><td></td></tr><tr><td>Stevens Tenotomy Scissors</td><td>Accurate Surgical &amp;amp; Scientific Instruments Corporation</td><td>ASSI.9193</td><td></td></tr><tr><td>Adson Forceps</td><td>Fine science tools</td><td>11006-12</td><td></td></tr><tr><td>Mosquito classic delicate hemostatic forceps</td><td>Codman</td><td>30-4472</td><td></td></tr><tr><td>Micro-retractor</td><td>Murdock; Roboz Surgical Instrument</td><td>RS-6550</td><td></td></tr><tr><td>Nonwoven gauze sponges</td><td>Fisherband</td><td>870-PC-DBL</td><td></td></tr><tr><td>Puritan 6&amp;rdquo; Small Cotton Swab w/Wooden Handle</td><td>Puritan Medical Products Company</td><td>868-WCS</td><td></td></tr><tr><td>Dumont SS Forceps - Standard Tips/Straight/Inox/13.5cm</td><td>Fine science tools</td><td>11203-23</td><td></td></tr><tr><td>Dumont SS Forceps - Standard Tips/Angled 45&amp;deg;/Inox/13.5cm</td><td>Fine science tools</td><td>11203-25</td><td></td></tr><tr><td>Vannas Spring Scissors - 3mm Cutting Edge</td><td>Fine science tools</td><td>15000-00</td><td></td></tr><tr><td>Microneedle holder</td><td>Aesculap Surgical Instruments</td><td>FD231R</td><td></td></tr><tr><td>Micro AROSuture, sterile 10-0 nylon suture, 70 &amp;micro;m, TAP points</td><td>AROSurgical Instruments Corporation</td><td>T4A10N07</td><td></td></tr><tr><td>4-0 Vicryl</td><td>Ethicon</td><td>J662H</td><td></td></tr><tr><td>5-ml Syringe</td><td>BD</td><td>309646</td><td></td></tr><tr><td>Falcon tissue culture dish, 60 &amp;times; 15 mm</td><td>Corning</td><td>353002</td><td></td></tr><tr><td>Isoflurane, United States Pharmacopeia (USP) liquid for inhalation, 250 ml</td><td>Piramal Healthcare</td><td>NDC 66794-017-25</td><td></td></tr><tr><td>Buprenex injectable (buprenorphine hydrochloride)</td><td>Reckitt Benckiser Pharmaceuticals</td><td>NDC 12496-0757-1</td><td></td></tr><tr><td>Cefazolin for injection , USP</td><td>APP Pharmaceuticals</td><td>NDC 63323-238-61</td><td></td></tr><tr><td>PVP scrub solution (povidone&amp;ndash;iodine 7.5%)</td><td>Medline</td><td>NDC 12496-0757-1</td><td></td></tr><tr><td>70% Ethanol</td><td>Decon Labs</td><td>2716</td><td></td></tr><tr><td>Phosphate Buffered Saline Without Calcium or Magnesium</td><td>LONZA</td><td>17-516F</td><td></td></tr><tr><td>Sirius Red</td><td>Sigma</td><td>365548</td><td></td></tr><tr><td>Hematolxylin</td><td>Fisher (Richard-Allan Scientific)</td><td>22-050-111 (7211)</td><td></td></tr><tr><td>Eosin</td><td>Anatech (Fisher)</td><td>832 (NC9686037)</td><td></td></tr><tr><td>Formalin</td><td>Fisher</td><td>SF100-20</td><td></td></tr></tbody></table>

partial bile duct ligation in the mouse: a controlled model of localized obstructive cholestasis

Em roedores, ligadura do colédoco completa (cBDL) do ducto biliar comum é uma técnica cirúrgica estabelecida para estudar a proliferação de colestase e ducto biliar obstrutiva. No entanto, as experiências a longo prazo podem levar a aumento da morbidade e mortalidade. Em cepas do mouse selecione com doença hepática subjacente, uma comparação significativa pode ser feita mesmo com ligadura de um único lóbulo do fígado, que pode reduzir as despesas e perdas de animais. Aqui, descrevemos a ligadura parcial de ducto biliar (pBDL) no rato, no qual é ligado somente à esquerda hepático ducto biliar, causando obstrução biliar no lobo esquerdo, mas não os lóbulos remanescentes. Com cuidado técnica microcirúrgica, experimentos de pBDL podem ser rentáveis, desde que o lobo unligated serve como um controle interno para os lóbulos ligados, quando submetidos às mesmas condições no mesmo animal. Ao contrário da cBDL, um grupo de controle de operação separado não é necessário. pBDL é altamente útil diretamente comparar localizada contra efeitos sistêmicos de colestase e outros componentes da bile retida. pBDL também pode ser reaproveitado como um novo método para investigar os mecanismos relacionados a medicamentos e a migração celular.

Para este experimento típico, pBDL foi realizado em ratos transgénicos triplicados PiZ, que recapitular a doença do fígado humana encontrada na deficiência de alfa-1 antitripsina (A1AT). O rato de PiZ overexpresses um transgene consiste em múltiplos fragmentos genomic do DNA que contêm as regiões codificação do gene humano mutante de A1AT e promotor, em conjunto com os intrões e ~ 2 kilobases de upstream e downstream flanqueiam regiões14, <s...

Watch this Scientific Journal Video about Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis at JoVE.com

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Aqui, apresentamos a ligadura parcial biliar como modelo cirúrgico de lesão hepática e regeneração em roedores.

Ligadura do colédoco parcial no Mouse: um modelo controlado da colestase obstrutiva localizada

In rodents, complete bile duct ligation (cBDL) of the common bile duct is an established surgical technique for studying obstructive cholestasis and bile ...

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Research

JoVE Journal

Biology

15.5K visualizações.  Jichi Medical University. Aqui, apresentamos a ligadura parcial biliar como modelo cirúrgico de lesão hepática e regeneração em roedores.

Vídeo: Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

Creation of Reversible Cholestatic Rat Model

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and affect the nutritional status and surgical outcomes. Study of the pathophysiological changes occurring in the liver and other organs is of importance. Various studies have been done in cholestatic rat models.
We used a reversible cholestatic rat model in our recent study looking at the role of methylprednisolone in the ischemia reperfusion injury. Various techniques for creation of a reversible cholestatic model have been described. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model.
This model can be used in various studies, such as looking at the changes in nutritional, physiological, pathological, histological and immunological changes in the gastrointestinal tract. This model can also be used to see the effects of cholestasis and various therapeutic interventions on major hepatic surgeries.

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model.

Criação de modelo Rat reversível colestática

Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and ...

Medicina

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration

Morphological organ regeneration following acute tissue loss is common among lower vertebrates, but is rarely observed in mammalian postnatal life. Adult liver regeneration after 70% partial hepatectomy results in hepatocyte hypertrophy with some replication in remaining lobes with restoration of metabolic activity, but with permanent loss of the injured lobe&#39;s morphology and architecture. Here, we detail a new surgical method in the neonate that leaves a physiologic environment conducive to regeneration. This model involves amputation of the left lobe apex and a subsequent conservative management regimen, and lacks the necessity for ligation of major liver vessels or chemical injury, leaving a physiologic environment where regeneration may occur. We extend this protocol to amputations on juvenile (P7-14) mice, during which the injured liver transitions from organ regeneration to compensatory growth by hypertrophy. The presented, brief 30 min protocol provides a framework to study the mechanisms of regeneration, its age-associated decline in mammals, and the characterization of putative hepatic stem or progenitors.

Here, we present a new method for partial resection of the left hepatic lobe in neonatal (day 0) mice. This new protocol is suitable for studying acute liver injury and injury response in the neonatal setting.

Hepatectomy parcial de Lobular: Um modelo cirúrgico para regeneração hepática morfológica

Morphological organ regeneration following acute tissue loss is common among lower vertebrates, but is rarely observed in mammalian postnatal life. Adult ...

Biologia do Desenvolvimento

Determining Bile Duct Density in the Mouse Liver

Mouse is broadly used as a model organism to study biliary diseases. To evaluate the development and function of the biliary system, various techniques are used, including serum chemistry, histological analysis, and immunostaining for specific markers. Although these techniques can provide important information about the biliary system, they often do not present a full picture of bile duct (BD) developmental defects across the whole liver. This is in part due to the robust ability of the mouse liver to drain the bile even in animals with significant impairment in biliary development. Here we present a simple method to calculate the average number of BDs associated with each portal vein (PV) in sections covering all lobes of mutant/transgenic mice. In this method, livers are mounted and sectioned in a stereotypic manner to facilitate comparison among various genotypes and experimental conditions. BDs are identified via light microscopy of cytokeratin-stained cholangiocytes, and then counted and divided by the total number of PVs present in liver section. As an example, we show how this method can clearly distinguish between wild-type mice and a mouse model of Alagille syndrome. The method presented here cannot substitute for techniques that visualize the three-dimensional structure of the biliary tree. However, it offers an easy and direct way to quantitatively assess BD development and the degree of ductular reaction formation in mice.

We present a rather simple and sensitive method for accurate quantification of bile duct density in the mouse liver. This method can aid in determining the effects of genetic and environmental modifiers and the effectiveness of potential therapies in mouse models of biliary diseases.

Determinando a densidade do ducto biliar no fígado do rato

Mouse is broadly used as a model organism to study biliary diseases. To evaluate the development and function of the biliary system, various techniques ...

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bile duct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bile duct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bile duct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.

Disruption of bile flow results in severe inflammatory cholestatic liver injury with a characteristic time-dependent sequence of morphological alterations. Here we present a protocol for the surgical ligation of the common bile duct in mice that allows to induce a strong fibrotic response after 21 to 28 days.

Ligadura do ducto biliar em ratos: Indução de Inflammatory Lesão hepática e fibrose por colestase obstrutiva

In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well ...

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia

Biliary atresia (BA) is a fatal disease involving obstructive jaundice, and it is the most common indication for liver transplantation in children. Due to the complex etiology and unknown pathogenesis, there are still no effective drug treatments. At present, the classic BA mouse model induced by rhesus rotavirus (RRV) is the most commonly used model for studying the pathogenesis of BA. This model is characterized by growth retardation, jaundice of the skin and mucosa, clay stools, and dark yellow urine. The histopathology shows severe liver inflammation and obstruction of the intrahepatic and extrahepatic bile ducts, which are similar to the symptoms of human BA. However, the livers of end-stage mice in this model lack fibrosis and cannot fully simulate the characteristics of liver fibrosis in clinical BA. The presented study developed a novel BA mouse model of chronic liver fibrosis by injecting 5-10 &#181;g of anti-Ly6G antibody four times, with gaps of 2 days after each injection. The results showed that some of the mice successfully formed chronic BA with typical fibrosis after the time lapse, meaning these mice represent a suitable animal model for the virus-induced liver fibrosis mechanistic study of BA and a platform for developing future BA treatments.

We established a mouse model of chronic liver fibrosis, which provides a suitable animal model for the virus-induced liver fibrosis mechanistic study of biliary atresia (BA) and a platform for future BA treatments.

Um Modelo Murino de Fibrose Hepática Crônica para o Estudo da Atresia Biliar

Biliary atresia (BA) is a fatal disease involving obstructive jaundice, and it is the most common indication for liver transplantation in children. Due to ...

Imunologia e Infecção

A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion

Chronic pancreatitis (CP) is a complex disease involving pancreatic inflammation and fibrosis, glandular atrophy, abdominal pain and other symptoms. Several rodent models have been developed to study CP, of which the bile duct 2,4,6 -trinitrobenzene sulfonic acid (TNBS) infusion model replicates the features of neuropathic pain seen in CP. However, bile duct drug infusion in mice is technically challenging. This protocol demonstrates the procedure of bile duct TNBS infusion for generation of a CP mouse model. TNBS was infused into the pancreas through the ampulla of Vater in the duodenum. This protocol optimized drug volume, surgical techniques, and drug handling during the procedure. TNBS-treated mice showed features of CP as reflected by bodyweight and pancreas weight reductions, changes in pain-associated behaviors, and abnormal pancreatic morphology. With these improvements, mortality associated with TNBS injection was minimal. This procedure is not only critical in generating pancreatic disease models but is also useful in local pancreatic drug delivery.

Chronic pancreatitis (CP) is a disease characterized by inflammation and fibrosis of the pancreas, often associated with intractable abdominal pain. This article focuses on refining the technique to generate a mouse model of CP via bile duct infusion with 2,4,6 -trinitrobenzene sulfonic acid (TNBS).

Um modelo de rato para pancreatite crônica através da infusão TNBS do ducto biliar

Chronic pancreatitis (CP) is a complex disease involving pancreatic inflammation and fibrosis, glandular atrophy, abdominal pain and other symptoms. ...

Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, cardiovascular events, and cancers) through restrictive and malabsorptive mechanisms. Understanding the mechanisms by which these procedures allow such improvements often require their transposition into animals, especially in mice, because of the ease of generating genetically modified animals. Recently, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has emerged as a procedure that uses both restrictive and malabsorptive effects, which is being used as an alternative to gastric bypass in case of major obesity. Thus far, this procedure has been associated with strong metabolic improvements, which has led to a marked increase in its use in daily clinical practice. However, the mechanisms underlying these metabolic effects have been poorly studied as a result of a lack of animal models. In this article, we present a reliable and reproducible model of SADI-S in mice, with a special focus on perioperative management. The description and use of this new rodent model will be helpful for the scientific community to better understand the molecular, metabolic, and structural changes induced by the SADI-S and to better define the surgical indications for clinical practice.

Single-anastomosis duodeno-ileal bypass (SADI-S) is an emerging bariatric procedure with important metabolic effects. In this article, we present a reliable and reproducible model of SADI-S in mice.

Modelo de Bypass Duodeno-Ileal de Anastomose Única com Gastrectomia Vertical em Camundongos

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes ...

<meta charset="utf8"></head><body>Estudando a regeneração hepática de ALLPS em modelos animais para hepatectomia estadiada

A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative mortality, severely impacting patient outcomes. In a robust hepatic environment, the future liver remnant (FLR) must exceed 25%, and in cases of cirrhosis, this requirement increases to over 40%. The inadequacy of FLR is currently a major obstacle in the progression of hepatic surgery.
Traditional methods to enhance FLR hypertrophy mainly focus on portal vein embolization (PVE), but its effectiveness is considerably limited. In recent years, there have been numerous reports on a novel biphasic hepatectomy method involving hepatic partitioning and portal vein ligation, known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ALPPS surpasses PVE in efficiently and considerably inducing FLR hypertrophy. However, the detailed mechanisms driving ALPPS-facilitated hepatic regeneration are not fully understood. Thus, replicating ALPPS in animal models is crucial to thoroughly investigate the molecular mechanisms of hepatic regeneration, offering valuable theoretical and practical insights.

<meta charset="utf8"></head><body>Autor em destaque: avançando na pesquisa de regeneração hepática por meio do modelo de camundongo ALPPS

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has been shown to result in remarkable liver regeneration after several weeks post first-stage surgery. Animal models that have undergone ALPPS have been developed to explore potential liver regeneration ability and achieve favorable clinical outcomes.

Um modelo de camundongo da partição hepática associada e ligadura da veia porta para procedimento de hepatectomia encenada auxiliado por microscopia

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative ...

Ligadura do colédoco parcial no Mouse: um modelo controlado da colestase obstrutiva localizada

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Ligadura do ducto biliar em ratos: Indução de Inflammatory Lesão hepática e fibrose por colestase obstrutiva

Um Modelo Murino de Fibrose Hepática Crônica para o Estudo da Atresia Biliar

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