【作者】 吴丹；

【导师】 吴毅平；

【作者基本信息】 华中科技大学 ， 外科学， 2011， 硕士

【摘要】 目的探讨袖状胃切除术(sleeve gastrectomy)对非肥胖2型糖尿病GK大鼠(Goto.Kakizaki rats)的摄食量、体重、血糖、血脂以及胃肠激素的影响。方法雄性自发性2型糖尿病(GK)大鼠23只,随机分为手术组(n=9)、假手术组(n=7)、饮食配对组(n=7)。手术组(SG组)行袖状胃切除术;假手术组(Sham-SG组)行胃体切开后直接缝合,胃组织不切除;饮食配对组(Pair Food组)每日给予定量饮食。连续监测各组大鼠的摄食量、体重变化情况;于术前及术后第2、4、6、8、10、14、24周采集各组大鼠的血液样本,离心取上清,测定空腹血糖(FBG),用酶联免疫吸附法测定血清胰岛素、胃肠激素水平,行葡萄糖耐量(OGTT)试验比较各组大鼠调节血糖的能力,以及测定血脂的变化。结果1.SG组大鼠术后摄食量比术前降低,于观察24周内一直维持低于术前(P<0.01),sham-SG组于术后每日平均摄食量高于SG组术后每日平均摄食量,具有统计学意义(P<0.01)。PF组的每日平均进食量是根据SG组大鼠术后每日平均进食量确定的,量为(20.8±1.9)g,与SG组相当。2.各组大鼠在观察期间体重在术后开始到术后2周下降,后又缓慢回升,直至整个观察期24周内体重都保持稳定增长的趋势。SG组大鼠的体重变化与同一时间点的sham-SG组比较,术后前3周内,体重的变化无明显差异,无统计学意义(P>0.05)。于术后第4周开始至术后24周,平均体重增量低于sham-SG组,有明显统计学意义(P<0.01);整个观察期24周内与PF组比较则无明显差异,无统计学意义(P>0.05)。3.SG组空腹血糖于手术后开始出现明显的下降,第6周到第10周维持在一稳定水平,后又稍稍回升,到14周维持在一稳定水平(P<0.05)低于术前,直到整个观察期间内。SG组术后的空腹血糖值是明显低于PF组和sham-SG组的,有明显统计学意义(P<0.01)。PF组和sham-SG组给予干预后的血糖值与之前相比无明显变化,无统计学意义(P>0.05)。4.SG组手术后第2周血糖的水平显著低于手术前,证明术后葡萄糖耐受明显改善,有统计学意义(P<0.01)。手术后2周曲线下面积AUC比手术前减少28.1% (p<0.01)。SG组手术后2周血糖值显著低于sham-SG组和PF组(p<0.01),曲线下面积比sham-SG组和PF组减少21%。sham-SG组和PF组血糖值变化不明显,无统计学意义(P>0.05)。5.空腹血清胰岛素于术前1周开始直至术后24周,在整个观察期内,SG组与sham-SG组之间的胰岛素变化无明显的统计学意义(P>0.05)。6.SG组血清ghrelin于术后开始下降,术后第2周下降到最低点,于术后4周维持在一稳定的水平(P<0.01)。Sham-SG组血清ghrelin水平于观察期间24周内并无明显变化,无统计学意义(P>0.05)。Sham-SG组的血清ghrelin水平与SG组的相比,术前无明显差异(P>0.05),术后则明显高于SG组的,有明显统计学意义(P<0.05)。7.SG组血清GLP-1水平于术后开始升高,直至术后第6周,维持在一稳定水平,一直保持高水平,SG组血清GLP-1水平在整个观察期24周内也显著高于Sham-SG组,有统计学意义(P<0.01 )。Sham-SG组的血清GLP-1水平于术前和术后整个观察期24周内无明显变化,无统计学意义(P>0.05)。8.SG组TG,TC低于sham-SG组,HDL高于sham-SG组,有统计学意义(P<0.01 )结论1.本实验成功的以非肥胖的2型糖尿病大鼠(GK大鼠)为对象,建立了袖状胃切除术模型(SG模型),探讨了SG对非肥胖的T2DM的治疗作用和相关的可能机制。袖状胃切除术后GK大鼠的体重术后2周开始保持稳定增长的趋势,表明对于非肥胖的GK大鼠,SG手术不会影响正常体重,大鼠体重稳定的增长。2.行袖状胃切除术后GK大鼠的血糖于术后就开始下降,且糖耐量明显改善,SG手术对糖尿病的治疗作用不依赖于体重和饮食的影响,而是有其他的作用机制。3.血清ghrelin水平显著降低和血清GLP-1水平显著升高,提示袖状胃切除术影响了这些胃肠道激素的水平,提示胃肠道激素的变化和血糖的改善有一定联系,手术可能通过影响某些胃肠道激素的改变而起到控制血糖的作用。4.袖状胃切除术对血脂代谢也能改善,能降低心血管疾病发生的危险因素,给以外科手段治疗2型糖尿病、代谢紊乱性疾病提供了一定的实验依据。更多还原

【Abstract】 Objective To study the effects of sleeve gastrectomy on food intake, body weight, GLU, serum lipid and gastrointestinal hormone in Goto-Kakizaki rats.Method Thirty male GK rats were randomly divided into three average groups, SG group with nine animals、Sham SG group with seven animals、Pair food group with seven animals. SG group was treated with sleeve gastrectomy. The Sham group only had stomach section and then sutured, Stomach tissue is not removed. Pair food group was treated with daily quantitative diet. Continuous monitoring the food intake and body weight in each group. Taking blood 1d pre-operation, 2w, 4w, 6w, 8w, 10w, 14w, 24w post-operation respectively. Then centrifuge the blood and reserve the upper serum. Determined on fasting blood glucose and blood lipid, ELISA was used to test the plasma levels of insulin and gastrointestinal hormone. OGTT was used to test the regulation of blood sugar. Result1. Food intake: Postoperation the SG group have an obvious smaller amount of food intake in 24 weeks(P<0.01). The food intake of the sham group was notable higher than the SG group(P<0.01). The food intake of the pair food group as same as postoperation of the SG group(20.8±1.9g).2. Body weight: The 3 groups have a weight loss until to week 2, and then a progressive increase steadily of weight was observed from week 2 to week 24. the average weight of SG group was lower than the sham group in the period from week 4 to week 24(P<0.01), while the pair food group have no difference(p>0.05).3. FBG: Postoperation the SG group have an obvious low level of fasting blood glucose in the period of 24 weeks(p<0.05), while the Sham group and the pair food group have no difference. the level of FBG in SG group was lower than PF group and Sham group(P<0.01).4. OGTT: glucose tolerance of the SG group was observed a remarkable improvement than the time of preoperation(P<0.01), while the Sham group and the pair food group have no difference(p>0.05). the AUC in 2nd week decreased by 28.1%(P<0.01), the level of blood glucose of the SG group after 2 week is obvious lower than PF group and Sham group(P<0.01), and the AUC of SG group is decreased by 21%(P<0.01), Compared with the Sham group and the pair food group.5. FISN: Serum insulin level of the 3 groups presented no remarkable change in 24 weeks(p>0.05).6.Ghrelin: Postoperation the SG group have an obvious reduce of the level of ghrelin(P<0.01), while the Sham group have no significant difference(p>0.05). Postoperation the level of ghrelin in SG group was obvious lower than Sham group(P<0.01),while the SG group and the Sham group have no significant difference pre-operation (p>0.05).7. GLP-1: The GLP-1 level of the SG group presented a continually high state and was significantly higher than the Sham group in 24 weeks(P <0.01). Postoperation the Sham group have no remarkable change (p>0.05).8. TG, TC, HDL: 10 weeks after operation, The TG and TC level of the SG group was obvious lower than Sham group(P<0.01), and The HDL level of the SG group was obvious higher than Sham group(P<0.01).Conclusion1. In this study, we investigated the effect of sleeve gastrectomy in non-obese type 2 diabetic rats. Postoperation of the SG, the weight of the rats increased steadily after 2 weeks, The results indicated that Sleeve gastrectomy will not affect the normal weight in non-obese type 2 diabetic rats, and there is a increase steadily of weight.2. After operation of SG, fasting blood glucose was significant reduced, and glucose tolerance of the SG group was observed a remarkable improvement, The study findings suggest that the therapeutic effect of SG in non-obese T2DM is not depend on weight and food intake, there are some other mechanism.3. Serum ghrelin were significantly reduced and Serum GLP - 1 were significantly increased, These indicating that the sleever gastrectomy affected these gastrointestinal hormone levels, and the change of these gastrointestinal hormone has certain relationships with blood glucose. sleever gastrectomy may be Play the role of controlling blood glucose by affecting these gastrointestinal hormone.4. lipid metabolism can be also improved by SG, and SG can reduce risk factors of cardioascular disease, this study provides certain experimental basis for the surgical treatment of type 2 diabetes and dysmetabolic syndrome.更多还原