单吻合口袖状胃切除联合十二指肠空肠旁路术在2型糖尿病大鼠模型中降糖、减重的研究

发布时间：2018-05-24 10:44

本文选题：2型糖尿病 + 袖状胃切除术　；参考：《第二军医大学》2017年硕士论文

【摘要】：我国20岁以上的人群糖尿病总体患病率为9.7%,患病总数高达9240万,位居世界第一,其中 2 型糖尿病(Type2diabeticmellitus,T2DM)占 90%。T2DM 作为一种传统的内科疾病,近年来最引入注目的治疗进展就是纳入了外科手术,美国糖尿病协会达成共识,将胃旁路手术(Roux-en-Y gastric bypass, RYGB)作为T2DM的治疗选择之一。袖状胃切除术(sleeve gastrectomy, SG)作为一种新型独立的减重手术,因其手术难度低,并发症少,在世界范围内得到了越来越多的应用。然而随着SG数量的增加,越来越多的外科医生关注SG的视角由减重转向其作为“代谢手术”的效果并对比其与“金标准”的RYGB在缓解T2DM疗效的差异,SG的效果并不完美。因此越来越多的外科医生选在一期手术时即对SG附加旁路成分。单吻合口袖状胃切除结合十二指肠-空肠旁路手术(Single-Anastomosis Duodenal-Jejunal Bypass with Sleeve Gastrectomy,SADJB-SG )在 2013 年首次由亚洲的外科医生所提出,SADJB-SG在短期的随访中,减重和缓解糖尿病的效果稳定,并且具有以下优点:(1)与RYGB相比,SADJB-SG避免了残胃癌的发生。(2) SADJB-SG可以认为是一种简化了的胆胰分流/十二指肠转位(biliopancreatic diversion with duodenal switch, BPD/DS),同时兼顾了袖状胃切除的优势和“前肠理论”和“后肠理论”。(3)RYGB和BPD/DS的不过术式均有两个吻合口,而SADJB-SG在保证基本原理不便的情况下减少了一个吻合口,这对手术操作难度、术后恢复以及并发症的发生均有提高。本研究拟建立一个安全可靠的SADJB-SG大鼠模型,并且在次模型的基础上进一步观察其减重及缓解T2DM的效果,初步探索SADJB-SG术后ghrelin和GLP-1等胃肠道激素的变化。第一部分单吻合口袖状胃切除联合十二指肠空肠旁路术在肥胖型T2DM大鼠模型中的建立研究目的在SG大鼠模型的基础上建立一个安全可靠的SADJB-SG大鼠模型,并且选择屈氏韧带下l0cm、20cm和30cm处行十二指肠空肠吻合。材料和方法100只6周龄清洁级Sqrague-Dawley大鼠(SD大鼠),体重150-180g,平均体质量173.66±13.73g,随机分为普通饲料组20只(NF组),平均体质量174.98±14.36g,高脂高糖饲料组80只(HF组),平均体质量173.33±13.164g,两组无统计学差异(p0.05)。所有大鼠饲养8周,HF组中体重大于NF组体重20%者定义为肥胖大鼠,最终HF组共70只达到体质量要求。达到体质量要求的HF组大鼠经腹腔一次性注射链脲佐菌素溶液(STZ) 45mg/kg,注射3天后经尾静脉测定血糖,连续三天内平均血糖大于16.70mmol/L者为造模成功者,最终共61只大鼠达到模型要求,造模成功率76.25%。排除手术死亡大鼠后共分为以下5组:空白对照组(SO组)10只,SG组10只,SADJB-SG组30只,后根据十二指肠的吻合位置又分为SA10组(吻合口位于屈氏韧带下10cm) 10只,SA20组10只,SA30组l0只。结果SG组大鼠共行手术12只,死亡2只,存活率为83.33%。SADJB-SG手术大鼠39只,死亡9只大鼠,手术存活率为76.92%。SG组、SA10组、SA20组和SA30组的手术时间分为别52.4±5.44分钟,69.2±5.41分钟,68.7±5.74分钟和68.2±5.55分钟,SG组的手术时间小于SADJB-SG各组的手术时间,具有统计学意义(p 0.05)。结论本研究成功建立了肥胖型T2DM大鼠模型和SADJB-SG大鼠模型,并且可以在次基础上进一步研究相关术式缓解肥胖和T2DM的效果。第二部分单吻合口袖状胃切除联合十二指肠空肠旁路术缓解肥胖型2型糖尿病大鼠的研究研究目的探索SADJB-SG缓解肥胖型T2DM大鼠的效果。材料和方法6周龄清洁级Sqrague-Dawley大鼠(SD大鼠),经过高脂高糖饲料喂养8周+一次性腹腔注射STZ溶液(45mg/kg)诱导为T2DM大鼠后共分为以下5组:空白对照组(S0组)10只,SG组10只,SADJB-SG组30只,后根据十二指肠的吻合位置又分为SA10组(吻合口位于屈氏韧带下10cm) 10只,SA20组10只,SA30组10只。通过OGTT检测大鼠空腹及餐后血糖和胰岛素,判断糖尿病缓解情况。通过高葡萄糖钳夹技术和正葡萄糖高胰岛素钳夹技术判断大鼠胰岛β细胞的功能和胰岛素敏感性。结果SG和SADJB-SG均可有效降低大鼠的空腹血糖和空腹胰岛素,以及OGTT血糖和胰岛素的曲线下面积。两者均可有效增加大鼠第一时相胰岛素分泌和第二时相胰岛素分泌,增加葡萄糖输注率,胰岛素敏感性指数明显增加,但SG和SADJB-SG之间差异不大。结论SG和SADJB-SG都可以显著降低T2DM大鼠的空腹血糖和空腹胰岛素水平,降低血糖和胰岛素的曲线下面积,改善胰岛素抵抗和胰岛素敏感性,增加第一时相和第二时相的胰岛素分泌。第三部分单吻合口袖状胃切除联合十二指肠空肠旁路术缓解肥胖和2型糖尿病机制的研究研究目的通过检测SADJB-SG术后血清ghrelin和GLP-1的变化,研究SADJB-SG缓解肥胖型T2DM可能的机制。材料和方法6周龄清洁级Sqrague-Dawley大鼠(SD大鼠),经过高脂高糖饲料喂养8周+一次性腹腔注射STZ溶液(45mg/kg)诱导为T2DM大鼠后共分为以下5组:空白对照组(SO组)10只,SG组10只,SADJB-SG组30只,后根据十二指肠的吻合位置又分为SA10组(吻合口位于屈氏韧带下10cm) 10只,SA20组10只,SA30组10只。在实验第一天(大鼠6周龄)、术前3天和术后8周检测空腹血清total ghrelin (TG)和Acylated ghrelin (AG),在术前3天和术后8周检测空腹、灌胃30分钟、60分钟和90分钟的血清GLP-1值。结果肥胖大鼠具有更低的血清TG值,但AG不变,AG/TG增高,SG和SADJB-SG可以进一步降低血清TG值,AG仍不变,AG/TG进一步增高。SADJB-SG可增加空腹和灌胃后的GLP-1浓度,尤其是灌胃后30分钟,SA30组具有最高的30分钟GLP-1浓度。结论SG和SADJB-SG均可以有效降低大鼠血清空腹TG浓度,但并不改变AG浓度,而AG/TG的比例进一步增高。SADJB-SG可以增加血清空腹GLP-1浓度,SG和SADJB-SG都可以明显增高灌胃30分钟后的GLP-1浓度,但后者增加幅度更大,且随着吻合口位置的增加,SADJB-SG对GLP-1的影响更大。
[Abstract]:The overall prevalence rate of diabetes in the population over 20 years old is 9.7%, the total number of diseases is 92 million 400 thousand and the world is the first. Among them, type 2 diabetes mellitus (Type2diabeticmellitus, T2DM) accounts for 90%.T2DM as a traditional medical disease. In recent years, the most notable progress of treatment is surgery. The American Diabetes Association has reached consensus. Roux-en-Y gastric bypass (RYGB) is one of the options for the treatment of T2DM. Sleeve gastrectomy (sleeve gastrectomy, SG), as a new type of independent weight reduction operation, has been used more and more in the world because of its low difficulty and less complications. However, as the number of SG increases, more and more out of the world. Doctors are concerned about the SG perspective from weight reduction to its effect as "metabolic surgery" and to compare its differences with the "gold standard" RYGB in alleviating T2DM efficacy. The effect of SG is not perfect. Therefore, more and more surgeons choose to add the accessory pathway to SG during the first phase of the operation. Single-Anastomosis Duodenal-Jejunal Bypass with Sleeve Gastrectomy, SADJB-SG) was first proposed by Asian surgeons in 2013. SADJB-SG has a stable effect on reducing and alleviating diabetes during short-term follow-up, and has the following advantages: (1) SADJB-SG avoids the occurrence of gastric stump cancer compared with RYGB. (2) SA DJB-SG can be considered a simplified biliary pancreatic shunt / duodenal transposition (biliopancreatic diversion with duodenal switch, BPD/DS), with both the advantages of sleeve gastrectomy and the "foregut theory" and "posterior gut theory". (3) there are two anastomotic stoma in RYGB and BPD/DS, while SADJB-SG ensures the basic principle. The difficulty of operation, postoperative recovery and complications were improved. A safe and reliable SADJB-SG rat model was established in this study. On the basis of the secondary model, the weight reduction and relieving effect of T2DM were further observed, and ghrelin and GLP-1 stomach after SADJB-SG were preliminarily explored. Changes in intestinal hormone. The first part of the single anastomotic sleeve gastrectomy combined with duodenal jejunostomy in the obese T2DM rat model, a safe and reliable SADJB-SG rat model was established on the basis of the SG rat model, and the duodenal jejunostomy was selected under the SG ligamentum ligamentum ligamentum, 20cm and 30cm. Materials and methods 100 6 week old clean Sqrague-Dawley rats (SD rats), weight 150-180g, average body mass of 173.66 + 13.73g, were randomly divided into 20 (NF) group of ordinary feed group (group NF), the average body mass was 174.98 + 14.36g, high fat high sugar diet group 80 (HF group), the average body mass was 173.33 + 13.164g, two groups had no statistical difference (P0.05). All rats were fed 8. The body weight of group HF in group HF was more than that of group NF, and the weight of group NF was defined as obese rats. In the final HF group, a total of 70 had body mass requirements. The group of rats reached the body mass requirement by intraperitoneal injection of streptozotocin solution (STZ) 45mg/kg, and 3 days after the injection, the blood glucose was measured by the tail vein, and the average blood sugar was greater than 16.70mmol/L within three days for the successful model success. A total of 61 rats reached the model requirements, and the success rate of the model was divided into 5 groups: 10 in the blank control group (group SO), 10 in group SG and 30 in group SADJB-SG, and then in SA10 group (10cm of the anastomotic mouth under the flexor ligament) according to the duodenal anastomosis position, 10 in SA20 group and l0 in SA30 group. The result SG was SG. In the group of rats, 12 rats were operated and 2 died. The survival rate was 39 83.33%.SADJB-SG rats, 9 rats died and the survival rate was 76.92%.SG. The operation time of group SA10, group SA20 and SA30 group was divided into 52.4 + 5.44 minutes, 69.2 + 5.41 minutes, 68.7 + 5.74 minutes and 68.2 + 5.55 minutes. The operation time of group SG was less than the operation of SADJB-SG groups. Time was statistically significant (P 0.05). Conclusion the obese T2DM rat model and SADJB-SG rat model were successfully established in this study, and the effect of related surgical treatment on obesity and T2DM could be further studied on the basis of this study. The second partial anastomotic sleeve gastrectomy combined with twelve finger jejunum bypass to alleviate Obesity Type 2 diabetes mellitus. The purpose of the study was to explore the effect of SADJB-SG on the release of obese T2DM rats. Materials and methods 6 weeks old clean Sqrague-Dawley rats (SD rats) were divided into 5 groups after 8 weeks of high fat and high glucose feed and STZ solution induced by intraperitoneal injection of STZ (45mg/kg) were divided into the following 5 groups: the blank control group (S0 group), and the SG group 10, SADJB-. Group SG 30, then according to the location of duodenal anastomosis, divided into group SA10 (10cm under the flexor ligamentum ligamentum), 10 in group SA20 and 10 in group SA30, to determine diabetic remission by OGTT test of fasting and postprandial blood glucose and insulin in rats. The rats were judged by hyperdextrose clamp technique and glucose high insulin clamp technique. The function of islet beta cells and insulin sensitivity. Results SG and SADJB-SG can effectively reduce the fasting blood glucose and fasting insulin in rats, as well as the area under the curve of OGTT blood glucose and insulin. Both can effectively increase the first phase insulin secretion and the second phase insulin secretion, increase the glucose infusion rate and insulin sensitivity. The sex index increased significantly, but there was little difference between SG and SADJB-SG. Conclusion both SG and SADJB-SG can significantly reduce the level of fasting blood glucose and fasting insulin in T2DM rats, reduce the area under the curve of blood glucose and insulin, improve insulin resistance and insulin sensitivity, and increase the insulin secretion in the first and second phase. The third part is increased. Study on the mechanism of obesity and type 2 diabetes by single anastomotic sleeve gastrectomy combined with duodenal jejunostomy in order to study the possible mechanism of SADJB-SG in alleviating obesity type T2DM by detecting the changes of serum ghrelin and GLP-1 after SADJB-SG. Materials and methods of high fat and high lipid level in clean grade Sqrague-Dawley rats (SD rats) at the age of 6 weeks 8 weeks and one-off intraperitoneal injection of STZ solution (45mg/kg) induced by sugar feed were divided into 5 groups: blank control group (group SO) 10, SG group 10 and SADJB-SG group 30, and then the duodenum anastomosis position was divided into SA10 group (the anastomotic mouth under the flexor ligament 10cm) 10, SA20 group 10, and SA30 group 10. In the first day of the experiment ( Total ghrelin (TG) and Acylated ghrelin (AG) of fasting serum were detected at 3 days before and 8 weeks after operation. The serum GLP-1 values were detected at 3 days before and 8 weeks after operation. The serum GLP-1 value was 30 minutes, 60 and 90 minutes. The results showed that the obese rats had lower serum TG value, but AG remained unchanged, AG/TG increased, SG and SADJB-SG could further reduce serum levels. The value of TG and AG remained unchanged, and the further increase of AG/TG in.SADJB-SG could increase the GLP-1 concentration in the fasting and after gavage, especially in the 30 minute after gavage, and the SA30 group had the highest GLP-1 concentration in 30 minutes. Conclusion SG and SADJB-SG could effectively reduce the concentration of TG in the fasting serum of rats, but did not change the AG concentration, but the proportion of AG/TG was increased. Adding serum fasting GLP-1 concentration, both SG and SADJB-SG could significantly increase the concentration of GLP-1 after 30 minutes of gastric perfusion, but the latter increased significantly, and with the increase of the location of the anastomosis, SADJB-SG had a greater impact on GLP-1.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1;R-332;R656.6

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