Summary

袖胃切除术的技术和改良的小鼠空肠Roux-en-Y胃旁路

Published: March 20, 2017
doi:

Summary

Bariatric surgery is the most efficient way to reduce body weight and the deadly metabolic complications (diabetes, obesity, and dyslipidemia) frequently associated with morbid obesity. Mouse models of bariatric surgery represent a unique asset for deciphering molecular mechanisms behind the beneficial effects of these surgeries on diabetes, hypertension, and dyslipidemia.

Abstract

肥胖是一个重大的公共健康问题,以4〜28%的男性和6.2〜36.5%的妇女在欧洲(2003年至2008年)患病。病态肥胖通常与代谢并发症,如2型糖尿病,高血压和血脂异常相关,降低寿命和质量。在没有任何有效的非侵入性的治疗,减肥手术是治疗病态肥胖(体重指数(BMI)“40公斤/米2)一个有价值的治疗选择,从而导致长期的,持续的代谢并发症体重减轻和改善。然而,维持减肥手术的有益效果的底层的细胞和分子机制尚未完全清楚。由于可用众多遗传修饰的菌株,所述的小鼠模型是最方便的动物模型,探讨背后减肥手术的多效性有益效果的分子机制。在这里,我们详细介绍了优化healthc是在小鼠中的两个最广泛使用的减肥手术的方法和手术的协议:该套筒胃和改性空肠Roux-en-Y胃旁路。破译底层减肥手术的治疗作用的分子机制提供了新的识别目标的疗法的承诺。

Introduction

肥胖和糖尿病的全球大流行病是在严重性毁灭性的。全球超过两十亿成年人(占总人口的30%)是超重(BMI> 25公斤/米2)或肥胖(BMI> 30公斤/米2)1。这可以与代谢的并发症,如2型糖尿病,高血压,和血脂异常一起走,导致增加的发病率和死亡率。肥胖会增加整体死亡率和癌症2的患病率。由于缺乏任何有效的无创治疗,减肥手术表示可以导致长期的,持续的体重减轻3,4是唯一的选择。许多不同的手术方法已被开发,但在套筒胃切除术(SG)和空肠Roux-en-Y胃旁路术(RYGB)是在临床实践中最常使用的两个过程。在SG过程,胃的初始体积的80%是拆除;因此,该技术是提高饱限制性手术之一。该RYGB是的制约,吸收不良的技术之一。 RYGB中,创建了一个小胃囊(总胃体积的1-2%)和肠被重新布置成Y形,其中延迟消化和营养物质的吸收。这两种技术导致显著体重减少和普遍改善在频繁相关的合并症( 例如,高血压,2型糖尿病和血脂异常)3,与RYGB看到一个更高的效率。然而,后面的减肥手术的多效性有益效果的分子机制常常没有完全阐明。由于可用的众多基因改造的菌株,小鼠模型是最方便的动物模型来研究这些分子机制。

然而,减肥手术很难直接适应小动物模型和requirË高外科灵巧。而SG可以容易地在啮齿类动物中具有很好的存活率进行RYGB是在小鼠致死因严重肠梗阻5。不同改性RYGB技术已经被提出来抵消这个问题,特别是oesojejunostomy 5。在这里,我们提出了另一种选择:无胃切除胃空肠造口。本变形RYGB再现大多数的人类中观察到的有益效果(即一个显著体重减少和在葡萄糖和脂质体内稳态的改善)。

此稿件旨在总结和讨论小鼠SG与RYGB的技术和实验细节,并促进这些程序与视频的帮助。具体的亮点将有关的术前和术后保健的协议,使维生素和铁缺乏减少优化进行。

Protocol

动物和住房:获取8周龄C57BL / 6雄性小鼠。在10周龄,给水C57BL / 6小鼠免费接入和高脂肪的饮食(DIO饮食:脂肪35%千卡,25.8%酪蛋白,1.30%的矿物AIN,1.30%的维生素,1.70%,磷酸氢钙,0.7 %碳酸钙,2.10%柠檬酸钾,0.026%胆碱酒石酸氢盐,8.9%蔗糖,0.384%胱氨酸,6.5%的纤维素,31.7%猪油,3.3%大豆油,和16.29%麦芽糖糊精)8(SG)或14(RYGB)之前的减肥手术周。促进体重增加,给专用于RYGB…

Representative Results

大体情况 平均手术时间为SG程序是49.3±1.5分钟。我们除去62.8±5.0毫克胃的,它代表了胃的约80%的百分比。没有老鼠在手术过程中或七天死亡。一个鼠标(7.1%)在11 日术后第二天死了,因为引起的牛黄胃梗阻。 平均手术时间为RYGB手术为89.1±2.8分钟。死亡率RY…

Discussion

为了克服肥胖的日益流行,第一减肥手术程序在20世纪60年代出现在美国。自那时以来,全世界每年进行的程序的数量仍增加,今天,这些技术代表了病态肥胖6的管理的最佳治疗选择。之间制定的程序,SG和RYGB是在临床实践4中使用的两种最常用的方法。动物模型,特别是啮齿动物,已被用于破译后面减肥手术后观察到的一般健康状况改善的机制。

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Divulgations

The authors have nothing to disclose.

Acknowledgements

We thank Gilles Mithieux and Aude Barataud (INSERM U1213, Lyon, France) and Marie Liabeuf and Stephanie Lemarchand-Minde (Animal facility, l’Institut du Thorax, Nantes, France) for their help with the animal care protocol. This work was supported by grants from La région des Pays de la Loire, the Fondation d’Avenir, and the Casden Bank. We would like to thank Catherine Postic, Fadila Benhamed and Michelle Caüzac from l’institut Cochin for their hospitality and their help during the filming process.

Materials

Drugs
High Fat diet DIO diet Safe
Isoflurane Forane Baxter
Buprenorphin Buprecare Animalcare
Marbofloxacine Marbocyl Vetoquinol
Ammonium iron citrate, vitamins PP-B12 Fercobsang Vetoquinol
Vitamins A-D3-E-K-B Vita Rongeur Virbac
NaCl 0,9% NaCl 0,9%
Povidone solution Betadine Scrub Betadine
Povidone solution Betadine Solution Betadine
Carboptol 980 NF Ocrygel TVM
Name References Company Comments
Sutures
Prolene® 8.0, 6,5 mm Ethicon
Prolene® 5.0, 13 mm Ethicon
Name References Company Comments
Surgical equipments
Scissors FST
Needle holder Olsen-Hegar FST
Micro scissors Vannas FST
Micro forceps  Graefe FST
Micro forceps curved Graefe FST
Curved micro needle holder Castroviejo FST
Hemostatic collagen compress Pangen Urgo
Absorbent underpads VWR
Name References Company Comments
Specific equipments
Hematology system  Hemavet 950FS Hemavet
Glucose strips and glucometer One touch Verio Life scan
Stereo microscope MZ6 Leica 

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Ayer, A., Borel, F., Moreau, F., Prieur, X., Neunlist, M., Cariou, B., Blanchard, C., Le May, C. Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice. J. Vis. Exp. (121), e54905, doi:10.3791/54905 (2017).

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