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垂直袖状胃切除术的小鼠模型

A Murine Model of Vertical Sleeve Gastrectomy.

作者信息

Garibay Darline, Cummings Bethany P

机构信息

Department of Biomedical Sciences, Cornell University.

Department of Biomedical Sciences, Cornell University;

出版信息

J Vis Exp. 2017 Dec 18(130):56534. doi: 10.3791/56534.

DOI:10.3791/56534
PMID:29286478
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5755614/
Abstract

Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is a surgery of the gastrointestinal tract that is performed for the purpose of weight loss. Bariatric surgery is currently the most effective long-term treatment for obesity. In addition to weight loss, bariatric surgery produces additional health benefits such as remission of type 2 diabetes, remission of hypertension, and decreased risk of developing certain types of cancer. The mechanisms beyond weight loss for these benefits remain incompletely defined. Therefore, animal models of bariatric surgery are being developed and validated to identify the mechanisms leading to these benefits, with the goal of improving understanding of gastrointestinal physiology and identifying new therapeutic targets. VSG has become the most commonly performed bariatric procedure in the clinic in the United States because it is highly effective at producing weight loss and metabolic improvement, and is simpler to perform than other bariatric procedures. Therefore, we have developed and validated a murine model of VSG. This murine VSG model recapitulates many of the effects of VSG seen in humans, including improved glucose and blood pressure regulation. The method is based on isolation of the stomach, ligation of gastric vessels, and removal of 70% of the stomach by transecting along the greater curvature of the stomach. We have successfully applied this surgical protocol to various genetically modified mouse lines to define the mechanistic contributors to the benefits of VSG. Furthermore, this murine VSG model has been combined with other surgical techniques, to achieve deeper mechanistic insight. Therefore, this is a simple and versatile model for studying gastrointestinal physiology and the health benefits of bariatric surgery.

摘要

减重手术,如垂直袖状胃切除术(VSG),是一种为减肥目的而实施的胃肠道手术。减重手术是目前治疗肥胖最有效的长期疗法。除了减肥外,减重手术还能带来其他健康益处,如2型糖尿病缓解、高血压缓解以及某些类型癌症的发病风险降低。这些益处中除体重减轻之外的机制仍未完全明确。因此,正在开发和验证减重手术的动物模型,以确定导致这些益处的机制,目标是增进对胃肠生理学的理解并确定新的治疗靶点。在美国临床中,VSG已成为最常实施的减重手术,因为它在减肥和改善代谢方面非常有效,而且比其他减重手术操作更简单。因此,我们开发并验证了一种VSG小鼠模型。这种小鼠VSG模型概括了人类VSG所见的许多效应,包括改善血糖和血压调节。该方法基于胃的分离、胃血管结扎以及沿胃大弯横断切除70%的胃。我们已成功将此手术方案应用于各种基因改造小鼠品系,以确定VSG益处的机制性促成因素。此外,这种小鼠VSG模型已与其他手术技术相结合,以实现更深入的机制洞察。因此,这是一个用于研究胃肠生理学和减重手术健康益处的简单且通用的模型。

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本文引用的文献

1
Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice.垂直袖状胃切除术可降低小鼠血压并减轻下丘脑内质网应激。
Dis Model Mech. 2017 Mar 1;10(3):235-243. doi: 10.1242/dmm.027474. Epub 2017 Jan 12.
2
β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.β细胞胰高血糖素样肽-1受体有助于垂直袖状胃切除术后糖耐量的改善。
Endocrinology. 2016 Sep;157(9):3405-9. doi: 10.1210/en.2016-1302. Epub 2016 Aug 8.
3
TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice.TGR5有助于小鼠垂直袖状胃切除术后的血糖调节改善。
Gut. 2017 Feb;66(2):226-234. doi: 10.1136/gutjnl-2015-309871. Epub 2015 Oct 28.
4
Laparoscopic sleeve gastrectomy leads the U.S. utilization of bariatric surgery at academic medical centers.在学术医疗中心,腹腔镜袖状胃切除术在美国减肥手术的应用中占主导地位。
Surg Obes Relat Dis. 2015 Sep-Oct;11(5):987-90. doi: 10.1016/j.soard.2015.02.008. Epub 2015 Feb 12.
5
Vertical sleeve gastrectomy restores glucose homeostasis in apolipoprotein A-IV KO mice.垂直袖状胃切除术可恢复载脂蛋白A-IV基因敲除小鼠的葡萄糖稳态。
Diabetes. 2015 Feb;64(2):498-507. doi: 10.2337/db14-0825. Epub 2014 Aug 25.
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FXR is a molecular target for the effects of vertical sleeve gastrectomy.FXR 是垂直袖状胃切除术作用的分子靶点。
Nature. 2014 May 8;509(7499):183-8. doi: 10.1038/nature13135. Epub 2014 Mar 26.
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Surgical management of obesity and the relationship to cardiovascular disease.肥胖的外科治疗及其与心血管疾病的关系。
Circulation. 2013 Feb 26;127(8):945-59. doi: 10.1161/CIRCULATIONAHA.112.103275.
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Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency.垂直袖状胃切除术在两种胰高血糖素样肽 1 受体缺乏症的遗传小鼠模型中是有效的。
Diabetes. 2013 Jul;62(7):2380-5. doi: 10.2337/db12-1498. Epub 2013 Feb 22.
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Health benefits of gastric bypass surgery after 6 years.胃旁路手术后 6 年的健康益处。
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