这项工作得到了中国国家自然科学基金资助82100982 F.L.的支持。

本研究中的动物程序由四川大学华西口腔医学院伦理委员会审查和批准（WCHSIRB-D-2017-041）。本研究使用成年C57BL / 6小鼠（参见 材料表）。该方案增加了右上颌第一磨牙 （M1） 的机械负荷，用于近中运动，其中通过骨吸收和骨形成的耦合诱导高度协调的骨重塑过程（图 1）。
1.术前准备
<ol><li>手术项目<ol><li>为手术准备以下手术物品:手术平台（图2A），紧固件（图2B），手术器械（图2C 和 补充图S1），正畸用品（图2C）和牙齿修复用品（图2D）。 注意: 定制的螺旋弹簧是定制的，当拉伸到 10 毫米时提供 10cN 的力。</li>
	</ol></li>
	<li>灭菌<ol><li>通过高压灭菌对手术器械进行消毒，并用紫外线照射对所有手术物品进行消毒至少30分钟。</li>
	</ol></li>
	<li>麻醉<ol><li>通过腹腔注射给予氯胺酮（100mg / kg）和地西泮（5mg / kg）麻醉小鼠。</li>
		<li>用棉棒将兽医软膏涂抹在小鼠的眼睛上，以避免眼睛干涩。</li>
		<li>只有当用镊子捏住老鼠的脚趾时鼠标没有反应时，才进行手术。</li>
	</ol></li>
</ol>2.手术过程
<ol><li>使用胶带将麻醉小鼠的四肢以仰卧位展开并用胶带粘贴到手术平台上。</li>
	<li>在头部上方的两侧钉一根 27 G 针，在腋窝下方的两侧钉另一根 27 G 针。</li>
	<li>用橡皮筋缠绕在上面的两根针和上门牙上，用另一根橡皮筋缠绕在另外两根针和下门牙上。改变针头位置以控制张开程度和嘴的方向（图3A）。 注意: 对于正畸牙齿移动操作，在 buccinator 完全收紧之前，请保持嘴巴最大张度。应将舌头拉向非手术侧，以暴露手术区域并防止缺血。</li>
	<li>弯曲 1.5 cm 304 不锈钢丝的 304 mm 端，并用弯曲的眼镊子将弯曲端从颊侧推过 M1 和上颌第二磨牙 （M2） 之间的相邻空间（图 3B）。当从腭侧看到结扎线的腭端时，将其拉出至其长度的一半左右，并将其穿过定制螺旋弹簧的一端。</li>
	<li>用结扎线的两端在上颌骨 M1 的近中方向打一个方形结，直到弹簧牢固地固定在牙齿上（图 3C）。减去多余的电线。</li>
	<li>同样，将第二根 3 cm 304 不锈钢丝穿过螺旋弹簧的另一端。</li>
	<li>用棉球清洁并擦干门牙表面。用棉棒在所有这些表面上涂上粘合剂并光固化。</li>
	<li>将第二根不锈钢丝推过上颌门牙之间的相邻空间，并在唇部打一个滑结（图3D）。减去多余的金属丝，使金属丝的其余部分靠近齿面。</li>
	<li>注入光固化树脂覆盖结和门牙;光固化树脂（图3E）。</li>
</ol>3.术后管理
<ol><li>手术后，腹膜内注射0.05mg/kg丁丙诺啡用于术后镇痛。</li>
	<li>将麻醉的小鼠放在37°C恒温电热毯上。当小鼠通过行走恢复意识时，将其放回单独的笼子中。</li>
	<li>由于手术后门牙的功能有限，请仅用软食代替常规硬饲料。</li>
	<li>每天检查正畸矫治器。如果在检查过程中观察到任何影响正畸力传导的情况，例如弹簧变形、弹簧松动和装置脱落，则应将小鼠排除在实验之外。</li>
	<li>为了保持实验的可比性，每天评估手术后小鼠的体重。任何体重减轻超过其术前体重30%的小鼠都必须被排除在实验之外。</li>
</ol>

小鼠上颌骨正畸模型骨重塑分析指南

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作者声明没有利益冲突。

本文试图逐步描述小鼠上颌骨模型上最简单的正畸牙齿运动方案，以研究机械负荷诱导的骨重塑的潜在机制。除了骨重塑的研究外，这种方法还有一些其他的主流应用:1）正畸牙齿运动加速的方法学研究;2）正畸根部吸收研究;3）正畸牙齿运动和疼痛的生物学机制;4）转基因模型研究。
与其他机械负荷相关治疗（如下颌牵引成骨术 37）相比，正畸牙齿运动是最...

骨骼是一种高度活跃的重建组织，在个体的一生中会调整其大小、形状和特性 1,2。除了荷尔蒙、衰老、营养和其他生物或生化因素3外，机械负荷是最具决定性因素的观点也得到了普遍接受4,5。在一些机械负荷异常的情况下，骨吸收和骨形成之间的不平衡可能导致异常的骨重塑和骨骼疾病。长期卧床休息或在太空飞行中存在微重力条件下的废用性骨质疏松症和骨质流失等骨骼疾病与异常机械负荷密切相关6,7,8。
机械负荷也被用于治疗骨骼相关疾病，如牵引治疗和正畸治疗。牵引治疗已被用于发育性疾病，如颅缝早闭和下颌骨发育不全 9,10，而正畸治疗已被广泛用于矫正异常的牙齿位置和任何咬合不正11。正畸治疗的核心也是机械负荷的管理。当骨组织承受机械负荷时，通过骨吸收和骨形成的耦合诱导高度协调的骨重塑过程，这可以移动牙齿以达到正畸目的12,13。
虽然正畸治疗在临床实践中得到了广泛的应用，但由于我们对机械负荷的生物学效应的认识有限，正畸治疗的结果是不可控的。为了克服这些局限性，已经建立了几种动物模型，如小鼠、大鼠、兔、猫、狗、猴和猪，以研究机械负荷诱导的骨重塑的潜在机制（表1）14,15,16,17,18,19,20,21,22,23,24，25、26、27、28、29、30、31、32。狗、猴子、猪等大型动物在正畸手术中比小动物有一些优势——它们有更多类似人类的牙齿和牙列，因此外科手术很容易在人类身上复制。此外，广阔的视野可以降低手术难度，并可以应用各种正畸方案33,34。然而，大型动物很难获得，导致与样本量相关的挑战，并且它们受到伦理限制35.此外，常规的提取程序和复杂的仪器使实验难以进行，因此很少使用大型动物。
在这种情况下，啮齿动物主要用于建立正畸模型。在这些模型中，与小鼠相比，大鼠和兔子的操作难度较低，牙齿运动方案更多。然而，小鼠模型具有独特的优势，即有大量转基因小鼠可用，这对于研究潜在机制尤为重要36。然而，小鼠模型是最难操作的模型，因为它的体积很小。回顾目前的方法，将第一磨牙沿近中方向移动是正畸模型的唯一实用方法。两个装置主要用于移动齿形螺旋弹簧和松紧带。使用松紧带比较容易，但正畸力变化很大，很难获得稳定的结果。
Xu等[15 ]建立了下颌骨上有螺旋弹簧的小鼠模型。然而，由于下颌骨的活动性和舌头的阻塞性，上颌骨手术始终是术中和术后考虑的首选。Taddei 等人 16 在 10 年前描述了鼠上颌骨的更详细方案，应该添加更多视觉和透明细节。综上所述，该方案系统地描述了小鼠上颌骨模型中详细的正畸牙齿运动方案，以帮助研究人员以标准化的方式掌握建模方法，并实现不同研究之间的比较评估。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Experimental Models: Mouse Lines</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>C57/B6J&#160;</td>
			<td>Gempharmatech Experimental Animals Company&#160;</td>
			<td>C57/B6J</td>
			<td></td>
		</tr>
		<tr>
			<td>Critical Commercial Assays</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hematoxylin and Eosin Stain Kit</td>
			<td>Biosharp</td>
			<td>BL700B</td>
			<td></td>
		</tr>
		<tr>
			<td>Masson&#8217;s Trichrome Stain Kit</td>
			<td>Solarbio</td>
			<td>G1340</td>
			<td></td>
		</tr>
		<tr>
			<td>Instruments</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>27 G needle</td>
			<td>Chengdu Xinjin Shifeng Medical Apparatus &#38; Instruments Co. LTD.</td>
			<td>SB1-074(IV)</td>
			<td></td>
		</tr>
		<tr>
			<td>Adhesives</td>
			<td>Minnesota Mining and Manufacturing Co., Ltd.</td>
			<td>41282</td>
			<td></td>
		</tr>
		<tr>
			<td>Corkboard</td>
			<td>DELI Group Co., Ltd.</td>
			<td>8705</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton balls</td>
			<td>Haishi Hainuo Group Co.,&#160; Ltd.</td>
			<td>20120047</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton sticks</td>
			<td>Lakong Medical Devices Co., Ltd.</td>
			<td>M6500R</td>
			<td></td>
		</tr>
		<tr>
			<td>Customized coil spring</td>
			<td>Chengdu Mingxing Spring Co., Ltd.</td>
			<td>1109-02</td>
			<td></td>
		</tr>
		<tr>
			<td>Forceps</td>
			<td>Chengdu Shifeng Co., Ltd.</td>
			<td>none</td>
			<td></td>
		</tr>
		<tr>
			<td>Light-cured fluid resin</td>
			<td>Shofu Dental Trading (SHANGHAI) Co., Ltd.</td>
			<td>518785</td>
			<td></td>
		</tr>
		<tr>
			<td>Light curer</td>
			<td>Liang Ya Dental Equipment Co., Ltd.</td>
			<td>LY-A180</td>
			<td></td>
		</tr>
		<tr>
			<td>Medical adhesive tapes&#160;</td>
			<td>Haishi Hainuo Group Co.,&#160; Ltd.</td>
			<td>0008-2014</td>
			<td></td>
		</tr>
		<tr>
			<td>Medical non-woven fabric</td>
			<td>Henan Yadu Industrial Co., Ltd.</td>
			<td>01011500018</td>
			<td></td>
		</tr>
		<tr>
			<td>Needle holders</td>
			<td>Chengdu Shifeng Co., Ltd.</td>
			<td>none</td>
			<td></td>
		</tr>
		<tr>
			<td>Rubber bands</td>
			<td>Haishi Hainuo Group Co.,&#160; Ltd.</td>
			<td>32X1</td>
			<td></td>
		</tr>
		<tr>
			<td>Surgical scissors</td>
			<td>Chengdu Shifeng Co., Ltd.</td>
			<td>none</td>
			<td></td>
		</tr>
		<tr>
			<td>Tweezers</td>
			<td>Chengdu Shifeng Co., Ltd.</td>
			<td>none</td>
			<td></td>
		</tr>
	</tbody>
</table>

the establishment of a murine maxillary orthodontic model

由于缺乏建立小鼠上颌骨正畸模型的可重复方案，我们提出了一个可靠且可重复的方案，为研究人员提供分析机械负荷相关骨重塑的可行工具。除了不同类型的原理图、操作照片和视频外，本研究还提供了详细的流程图。我们对 11 只成年宽型 C57/B6J 小鼠进行了该方案，并在术后第 3、8 和 14 天收获了样品。显微CT和组织病理学数据已经证明了使用该协议进行牙齿移动与骨重塑相结合的成功。此外，根据第3天、第8天和第14天的显微CT结果，我们将骨建模分为三个阶段:准备阶段、骨吸收阶段和骨形成阶段。这些阶段有望帮助关注不同阶段的研究人员合理地设置样本采集时间。该协议可以为研究人员提供一种工具，以进行骨重塑的再生分析。

我们已经对 11 只成年雄性小鼠（C57/BL6,3 个月大）进行了 OTM 手术。他们在手术后第 3、8 和 14 天被安乐死。在这些实验中，右上颌侧是手术侧，而左上颌侧是控制侧。显微CT显示，术后第3、8和14天，M1和M2之间的距离在时间上连续增加:分别为30μm、70μm和110μm（图4）。由于机械负荷，低密度牙周韧带在远端变宽，在根部近中侧变窄（图5）。此外，牙周?...

Watch this Scientific Journal Video about Author Spotlight: Insights into an Efficient Murine Maxillary Orthodontic Model Protocol at JoVE.com

作者聚焦:深入了解高效的小鼠上颌正畸模型方案

在这里，我们逐步演示了在小鼠上颌骨模型上操作的可管理的正畸牙齿运动方案。通过对每个步骤的明确解释和视觉演示，研究人员可以掌握该模型，并通过一些修改将其应用于他们的实验需求。

小鼠上颌骨正畸模型的建立

Due to the lack of reproducible protocols for establishing a murine maxillary orthodontic model, we present a reliable and reproducible protocol to ...

正如我们所回顾的，小鼠上颌正畸模型被广泛使用，但只是简单地描述。基于当前方法，很难在不同研究之间重复和比较实验数据。因此，该协议将帮助研究人员以标准化的方式掌握建模方法，并实现不同研究之间的比较评估。该协议实际上是迄今为止在小鼠中最简单的建模方法，我们的视频展示了许多实用的建模细节。这种方法以鼠为主，狭窄的操作空间肯定会给初学者带来很大的挑战。一定程度的练习可能会有所帮助。该协议以最简单的方式提供正畸负荷，因此该协议的实验将节省时间且易于重复。对于新手来说也有很多优势，例如手术视野开阔，视觉外科手术。零基学习者可以通过我们的协议更容易掌握这个模型。

the-establishment-of-a-murine-maxillary-orthodontic-model

Research

JoVE Journal

Medicine

The Establishment of a Murine Maxillary Orthodontic Model

573 次观看.  Sichuan University. 正如我们所回顾的，小鼠上颌正畸模型被广泛使用，但只是简单地描述。基于当前方法，很难在不同研究之间重复和比较实验数据。因此，该协议将帮助研究人员以标准化的方式掌握建模方法，并实现不同研究之间的比较评估。该协议实际上是迄今为止在小鼠中最简单的建模方法，我们的视频展示了许多实用的建模细节。这种方法以鼠为主，狭窄的操作空间肯定会给初?...

视频: 作者聚焦:深入了解高效的小鼠上颌正畸模型方案

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

A murine model of cutaneous wound healing that can be used to assess therapeutic compounds in physiological and pathophysiological settings.

伤口愈合的小鼠模型

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. ...

科研

医学

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

蛛网膜下腔出血的小鼠模型

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

Minimally Invasive Establishment of Murine Orthotopic Bladder Xenografts

Orthotopic bladder cancer xenografts are the gold standard to study molecular cellular manipulations and new therapeutic agents&#160;in vivo. Suitable cell lines are inoculated either by intravesical instillation (model of nonmuscle invasive growth) or intramural injection into the bladder wall (model of invasive growth). Both procedures are complex and highly time-consuming. Additionally, the superficial model has its shortcomings due to the lack of cell lines that are tumorigenic following instillation. Intramural injection, on the other hand, is marred by the invasiveness of the procedure and the associated morbidity for the host mouse.
With these shortcomings in mind, we modified previous methods to develop a minimally invasive approach for creating orthotopic bladder cancer xenografts. Using ultrasound guidance we have successfully performed percutaneous inoculation of the bladder cancer cell lines UM-UC1, UM-UC3 and UM-UC13 into 50 athymic nude. We have been able to demonstrate that this approach is time efficient, precise and safe. With this technique, initially a space is created under the bladder mucosa with PBS, and tumor cells are then injected into this space in a second step. Tumor growth is monitored at regular intervals with bioluminescence imaging and ultrasound. The average tumor volumes increased steadily in in all but one of our 50 mice over the study period.
In our institution, this novel approach, which allows bladder cancer xenograft inoculation in a minimally-invasive, rapid and highly precise way, has replaced the traditional model.

The established technique to inoculate primary invasive orthotopic bladder cancer xenografts requires laparotomy and mobilization of the bladder. This procedure inflicts significant morbidity on the mice, is technically challenging and time-consuming. We therefore developed a high-precision, percutaneous approach utilizing ultrasound guidance.

微创建立小鼠原位膀胱移植瘤的

Orthotopic bladder cancer xenografts are the gold standard to study molecular cellular manipulations and new therapeutic agents&#160;in vivo. Suitable ...

A Preclinical Murine Model of Hepatic Metastases

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, murine pancreatic tumor model of hepatic metastases via a hemispleen injection of syngeneic murine pancreatic tumor cells is described. This model mimics many of the clinical conditions in patients with metastatic disease to the liver. Mice consistently develop metastases in the liver allowing for investigation of the metastatic process, experimental therapy testing, and tumor immunology research.

A preclinical, murine model of hepatic metastases performed via a hemispleen injection technique.

肝转移的临床前小鼠模型

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia

Critical limb ischemia (CLI) is a serious condition that entails a high risk of lower limb amputation. Despite revascularization being the gold-standard therapy, a considerable number of CLI patients are not suited for either surgical or endovascular revascularization. Angiogenic therapies are emerging as an option for these patients but are currently still under investigation. Before application in humans, those therapies must be tested in animal models and its mechanisms must be clearly understood. An animal model of hindlimb ischemia (HLI) has been developed by the ligation and excision of the distal external iliac and femoral arteries and veins in mice. A comprehensive panel of tests was assembled to assess the effects of ischemia and putative angiogenic therapies at functional, histologic and molecular levels. Laser Doppler was used for the flow measurement and functional assessment of perfusion. Tissue response was evaluated by the analysis of capillary density after staining with the anti-CD31 antibody on histological sections of gastrocnemius muscle and by measurement of collateral vessel density after diaphonization. Expression of angiogenic genes was quantified by RT-PCR targeting selected angiogenic factors exclusively in endothelial cells (ECs) after laser capture microdissection from mice gastrocnemius muscles. These methods were sensitive in identifying differences between ischemic and non-ischemic limbs and between treated and non-treated limbs. This protocol provides a reproducible model of CLI and a framework for testing angiogenic therapies.

Here, a critical hindlimb ischemia experimental model is presented followed by a battery of functional, histologic and molecular tests&#160;to assess the effectiveness of angiogenic therapies.&#8203;

评估下肢缺血的Murine模型的治疗血管生成

Critical limb ischemia (CLI) is a serious condition that entails a high risk of lower limb amputation. Despite revascularization being the gold-standard ...

Establishment of a Severe Dry Eye Model Using Complete Dacryoadenectomy in Rabbits

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer&#39;s tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.

A novel approach is presented to induce chronic dry eye disease in rabbits by surgically removing all orbital lacrimal glands. This method, distinct from those previously reported, produces a stable, reproducible model of aqueous deficient dry eye well suited to study tear physiology and pathophysiology and ocular therapeutics.

在兔子中使用完全的白眼切除术建立严重干眼模型

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic ...

3D Imaging of PDL Collagen Fibers during Orthodontic Tooth Movement in Mandibular Murine Model

Orthodontic tooth movement is a complex biological process of altered soft and hard tissue remodeling as a result of external forces. In order to understand these complex remodeling processes, it is critical to study the tooth and periodontal tissues within their 3D context and therefore minimize any sectioning and tissue artefacts. Mouse models are often utilized in developmental and structural biology, as well as in biomechanics due to their small size, high metabolic rate, genetics and ease of handling. In principle this also makes them excellent models for dental related studies. However, a major impediment is their small tooth size, the molars in particular. This paper is aimed at providing a step by step protocol for generating orthodontic tooth movement and two methods for 3D imaging of the periodontal ligament fibrous component of a mouse mandibular molar. The first method presented is based on a micro-CT setup enabling phase enhancement&#160;imaging of fresh collagen tissues. The second method is a bone clearing method using ethyl cinnamate that enables imaging through the bone without sectioning and preserves endogenous fluorescence. Combining this clearing method with reporter mice like Flk1-Cre;TdTomato provided a first of its kind opportunity to image the 3D vasculature in the PDL and alveolar bone.

We present a protocol for generating orthodontic tooth movement in mice and methods for 3D visualization of the collagen fibers and blood vessels of periodontal ligament without sectioning.

曼迪布勒穆林模型中矫形牙齿运动期间 PDL 胶原蛋白纤维的 3D 成像

Orthodontic tooth movement is a complex biological process of altered soft and hard tissue remodeling as a result of external forces. In order to ...

Establishment of a Mouse Severe Acute Pancreatitis Model using Retrograde Injection of Sodium Taurocholate into the Biliopancreatic Duct

The prevalence of acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is increasing in younger age groups annually. However, there is a lack of effective treatments in the current clinical practice. With the easy accessibility of transgenic and knockout strains and their small size, which allows minimal doses of drugs required for in vivo evaluation, a well-established experimental model in mice is preferred for AP research. Moreover, SAP induced through sodium taurocholate (TC) is currently one of the most widely used and best characterized models. This model has been investigated for novel therapies and possible molecular events during the process of AP. Here, we present the generation of an AP mouse model using sodium taurocholate and a simple homemade microsyringe. Moreover, we also provide the methodology for the subsequent histology and serological testing.

A mouse model of severe acute pancreatitis is described herein. The procedure presented here is very rapid, simple, and accessible, thereby potentially allowing the study of the molecular mechanisms and different therapeutic interventions in acute pancreatitis in a convenient way.

建立小鼠重症急性胰腺炎模型，将牛磺胆酸钠逆行注射到胆胰管中

The prevalence of acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is increasing in younger age groups annually. However, there is a ...

Establishment and Evaluation of a Porcine Vein Graft Disease Model

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the investigation of disease mechanisms and the development of therapeutic strategies. 
To perform the surgery, we enter the cardiac chamber through the third intercostal space and carefully dissect the internal mammary vein and immerse it in normal saline. The right main coronary artery is then treated for ischemia. The target vessel is incised, a shunt plug is placed, and the distal end of the graft vein is anastomosed. The ascending aorta is partially blocked, and the proximal end of the graft vein is anastomosed after perforation. The graft vein is checked for patency, and the proximal right coronary artery is ligated. 
CABG surgery is performed in minipigs to harvest the left internal mammary vein for its use as a vascular graft. Serum biochemical tests are used to evaluate the physiological status of the animals after surgery. Ultrasound examination shows that the proximal, middle, and distal end of the graft vessel are unobstructed. In the surgical model, turbulent blood flow in the graft is observed upon histological examination after the CABG surgery, and venous graft stenosis associated with intimal hyperplasia is observed in the graft. The study here provides detailed surgical procedures for the establishment of a repeatable CABG-induced VGD model.

In this protocol, novel pig vein bypass grafting was performed through a small incision in the left chest wall without cardiopulmonary bypass. A postoperative pathology study was done, which showed intimal thickening.