Name: use of animal model of sepsis to evaluate novel herbal therapies
Uploaded: 2012-04-11T13:00:00
Description: Watch this Scientific Journal Video about Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies at JoVE.com

Dette arbeidet ble støttet med tilskudd fra National Institutes of Health, National Institute of General Medical Science (R01GM063075) og National Center of komplementær og alternativ medisin (R01AT05076).

1. Etablering av Animal Model of Sepsis <ol><li> Mus er bedøvet med ketamin (75 mg / kg, intramuskulært, im) og xylazin (10 mg / kg, im), og plasseres i ryggleie. </li><li> Fest føttene på musen med tape for å sikre en stabil posisjon. </li><li> Rengjør magen med 3 vekslende scrubs av Betadine eller annen hud desinfeksjonsmiddel og alkohol. Deretter lage en 15 mm midtlinjen innsnitt for å avsløre cecum. </li><li> Ligate cecum med en 4-0 silke sutur ved ca 5,0 mm fra cecal spissen, og deretter punktere ligated ...

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	<li>Wichterman, K. A., Baue, A. E., Chaudry, I. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sepsis+and+septic+shock--a+review+of+laboratory+models+and+a+proposal.">Sepsis and septic shock--a review of laboratory models and a proposal.</a> J. Surg. Res. 29, 189-201 (1980).</li><li>Baker, C. C., Chaudry, I. H., Gaines, H. O., Baue, A. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+factors+affecting+mortality+rate+after+sepsis+in+a+murine+cecal+ligation+and+puncture+model.">Evaluation of factors affecting mortality rate after sepsis in a murine cecal ligation and puncture model.</a> Surgery. 94, 331-335 (1983).</li><li>Hubbard, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cecal+ligation+and+puncture.">Cecal ligation and puncture.</a> Shock. 24, 52-57 (2005).</li><li>Akira, S., Takeda, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toll-like+receptor+signalling.">Toll-like receptor signalling.</a> Nat. Rev. Immunol. 4, 499-511 (2004).</li><li>Baggiolini, M., Loetscher, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemokines+in+inflammation+and+immunity.">Chemokines in inflammation and immunity.</a> Immunol. Today. 21, 418-420 (2000).</li><li>Balkwill, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cytokines--soluble+factors+in+immune+responses.">Cytokines--soluble factors in immune responses.</a> Curr. Opin. Immunol. 1, 241-249 (1988).</li><li>Wang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HMG-1+as+a+late+mediator+of+endotoxin+lethality+in+mice.">HMG-1 as a late mediator of endotoxin lethality in mice.</a> Science. 285, 248-251 (1999).</li><li>Yang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversing+established+sepsis+with+antagonists+of+endogenous+high-mobility+group+box+1.">Reversing established sepsis with antagonists of endogenous high-mobility group box 1.</a> Proc. Natl. Acad. Sci. U.S.A. 101, 296-301 (2004).</li><li>Qin, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+HMGB1+in+apoptosis-mediated+sepsis+lethality.">Role of HMGB1 in apoptosis-mediated sepsis lethality.</a> J. Exp. Med. 203, 1637-1642 (2006).</li><li>Ray, A., Dittel, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Isolation+of+Mouse+Peritoneal+Cavity+Cells.">Isolation of Mouse Peritoneal Cavity Cells.</a> J. Vis. Exp. (35), e1488 (2010).</li><li>Rendon-Mitchell, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IFN-gamma+Induces+High+Mobility+Group+Box+1+Protein+Release+Partly+Through+a+TNF-Dependent+Mechanism.">IFN-gamma Induces High Mobility Group Box 1 Protein Release Partly Through a TNF-Dependent Mechanism.</a> J. Immunol. 170, 3890-3897 (2003).</li><li>Li, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Major+Ingredient+of+Green+Tea+Rescues+Mice+from+Lethal+Sepsis+Partly+by+Inhibiting+HMGB1.">A Major Ingredient of Green Tea Rescues Mice from Lethal Sepsis Partly by Inhibiting HMGB1.</a> PLoS ONE. 2, e1153 (2007).</li><li>Osuchowski, M. F., Welch, K., Siddiqui, J., Remick, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circulating+cytokine/inhibitor+profiles+reshape+the+understanding+of+the+SIRS/CARS+continuum+in+sepsis+and+predict+mortality.">Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality.</a> J. Immunol. 177, 1967-1974 (2006).</li><li>Heuer, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+protein+C+and+other+biomarkers+as+predictors+of+mortality+in+a+rat+cecal+ligation+and+puncture+model+of+sepsis.">Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis.</a> Crit. Care. Med. 32, 1570-1578 (2004).</li><li>Bozza, F. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cytokine+profiles+as+markers+of+disease+severity+in+sepsis:+a+multiplex+analysis.">Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis.</a> Crit. Care. 11, R49 (2007).</li><li>Li, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EGCG+stimulates+autophagy+and+reduces+cytoplasmic+HMGB1+levels+in+endotoxin-stimulated+macrophages.">EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages.</a> Biochem. Pharmacol. 81, 1152-1163 (2011).</li><li>Beutler, B., Milsark, I. W., Cerami, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Passive+immunization+against+cachectin/tumor+necrosis+factor+protects+mice+from+lethal+effect+of+endotoxin.">Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin.</a> Science. 229, 869-871 (1985).</li><li>Tracey, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anti-cachectin/TNF+monoclonal+antibodies+prevent+septic+shock+during+lethal+bacteraemia.">Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia.</a> Nature. 330, 662-664 (1987).</li><li>Eskandari, M. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anti-tumor+necrosis+factor+antibody+therapy+fails+to+prevent+lethality+after+cecal+ligation+and+puncture+or+endotoxemia.">Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia.</a> J. Immunol. 148, 2724-2730 (1992).</li><li>Ziegler, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+gram-negative+bacteremia+and+septic+shock+with+HA-1A+human+monoclonal+antibody+against+endotoxin.+A+randomized,+double-blind,+placebo-controlled+trial.+The+HA-1A+Sepsis+Study+Group.">Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group.</a> N. Engl. J. Med. 324, 429-436 (1991).</li><li>Ziegler, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+gram-negative+bacteremia+and+shock+with+human+antiserum+to+a+mutant+Escherichia+coli.">Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli.</a> N. Engl. J. Med. 307, 1225-1230 (1982).</li><li>Abraham, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+and+safety+of+monoclonal+antibody+to+human+tumor+necrosis+factor+alpha+in+patients+with+sepsis+syndrome.+A+randomized,+controlled,+double-blind,+multicenter+clinical+trial.+TNF-alpha+MAb+Sepsis+Study+Group.">Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group.</a> JAMA. 273, 934-941 (1995).</li><li>Cohen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adjunctive+therapy+in+sepsis:+a+critical+analysis+of+the+clinical+trial+programme.">Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme.</a> Br. Med. Bull. 55, 212-225 (1999).</li><li>Dellinger, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surviving+Sepsis+Campaign:+international+guidelines+for+management+of+severe+sepsis+and+septic+shock:+2008.">Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.</a> Crit. Care Med. 36, 296-327 (2008).</li><li>Wang, H., Zhu, S., Zhou, R., Li, W., Sama, A. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapeutic+potential+of+HMGB1-targeting+agents+in+sepsis.">Therapeutic potential of HMGB1-targeting agents in sepsis.</a> Expert. Rev. Mol. Med. 10, e32 (2008).</li><li>Wang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+aqueous+extract+of+a+popular+herbal+nutrient+supplement,+Angelica+sinensis,+protects+mice+against+lethal+endotoxemia+and+sepsis.">The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis.</a> J. Nutr. 136, 360-365 (2006).</li><li>Li, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+cardiovascular+drug+rescues+mice+from+lethal+sepsis+by+selectively+attenuating+a+late-acting+proinflammatory+mediator,+high+mobility+group+box+1.">A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1.</a> J. Immunol. 178, 3856-3864 (2007).</li><li>Fukuyama, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mixed+bacterial+infection+model+of+sepsis+in+rabbits+and+its+application+to+evaluate+superantigen-adsorbing+device.">Mixed bacterial infection model of sepsis in rabbits and its application to evaluate superantigen-adsorbing device.</a> Blood Purif. 23, 119-127 (2005).</li></ol>

I laboratoriet har flere dyremodeller av sepsis blitt ansatt for å forstå patogenesen av sepsis for å utvikle potensielle nye behandlingsformer. Deres kliniske relevansen er fortsatt gjenstand for debatt før den vellykkede oversettelse av dyrestudier til kliniske applikasjoner for sepsis. Selv nøytraliserende antistoffer mot tidlig cytokiner (f.eks TNF) var beskyttende i dyremodeller av bakteriemi / endotoxemia 17,18, de faktisk forverre overlevelse i dyremodell av sepsis 19. Tilsvarende misly...

<table border="1"><tbody><tr><td> Navn på reagensen </td><td> Firma </td><td> Katalognummer </td></tr><tr><td> Betadine </td><td> Purdue Produkter LP </td><td> 25655-41-8 </td></tr><tr><td> imipenem </td><td> Merck &amp; Co, Inc. </td><td> 9882821 </td></tr><tr><td> Ketamin HCl </td><td> Hospira Inc. </td><td> RL-0065 </td></tr><tr><td> Xylazin </td><td> Lloyd Laboratories </td><td> 4821 </td></tr><tr><td> Autoclip </td><td> Becton Dickinson </td><td> 427631 </td></tr><tr><td> 4-0 silke sutur </td><td> Roboz </td><td> SUT-15-2 </td></tr><tr><td> Surflo IV kateter </td><td> TERUMO </td><td> SR * OX2419CA </td></tr><tr><td> RayBio mus cytokin antistoff matrise </td><td> RayBiotech, Inc. </td><td> AAM-CYT-3 </td></tr><tr><td> Thioglycollate </td><td> Becton Dickinson </td><td> 211716 </td></tr></tbody></table>

use of animal model of sepsis to evaluate novel herbal therapies

Sepsis refererer til en systemisk inflammatorisk respons syndrom som følge av mikrobiell infeksjon. Det har vært rutinemessig simulert i dyr av flere teknikker, inkludert tilførsel av eksogent bakteriell toksin (endotoxemia) eller bakterier (bakteriemi), samt kirurgisk perforering av cecum ved cecal ligation og punktering (CLP) 1-3. CLP tillater bakterier søl og fecal forurensing av bukhulen, etterligne menneskelige klinisk sykdom av perforert appendisitt eller divertikulitt. Alvorlighetsgraden av sepsis, som reflekteres av de eventuelle dødelighet, kan kontrolleres kirurgisk ved å variere størrelsen på nålen brukes for cecal punktere to. I dyr, induserer CLP lignende, bifasisk hemodynamiske kardiovaskulære, metabolske, og immunologiske responser som observeres under det kliniske forløpet av menneskelig sepsis tre. Dermed er CLP-modellen regnet som en av de mest klinisk relevante modeller for eksperimentell sepsis 1-3. &lt;/ P&gt; Ulike dyremodeller blitt brukt til å belyse de intrikate mekanismene bak patogenesen av eksperimentelle sepsis. Den dødelige konsekvensen av sepsis skyldes dels en overdreven opphopning av tidlige cytokiner (for eksempel TNF, IL-1 og IFN-γ) 4-6 og sent proinflammatoriske mediatorer (f.eks HMGB1) 7. Sammenlignet med tidlige proinflammatoriske cytokiner, sent langtidsvirkende meklere har en bredere terapeutisk vindu for kliniske applikasjoner. For eksempel, forsinket administrasjon av HMGB1-nøytraliserende antistoffer som begynner 24 timer etter CLP, likevel reddet mus fra letalitet 8,9, etablere HMGB1 som en sen formidler av dødelig sepsis. Funnet av HMGB1 som en sen-fungerende Mekleren har igangsatt et nytt felt med etterforskning for utvikling av sepsis terapier som bruker tradisjonell kinesisk urtemedisin. I denne artikkelen beskriver vi en prosedyre for CLP-indusert sepsis, og bruken i screening urtemedisin for HMGB1 målretting terapier.

Watch this Scientific Journal Video about Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies at JoVE.com

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Sepsis refererer til en systemisk inflammatorisk respons syndrom som følge av en mikrobiell infeksjon, og kan være simulert av en kirurgisk teknikk kalt cecal ligation og punktering (CLP). Her beskriver vi en metode for å bruke CLP-indusert dyremodell for å skjerme medisinske urter for terapeutiske agenter.

Bruk av Animal Model of Sepsis å evaluere Novel urteterapi

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several ...

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