糖尿病大鼠袖状胃切除术后胃肠动力改变及对GLP-1分泌的影响

发布时间：2018-07-11 13:44

  本文选题：代谢手术 + 减重手术　； 参考：《第二军医大学》2017年硕士论文

【摘要】：研究背景:肥胖和2型糖尿病已成为我国乃至全球主要的医疗卫生问题。新型代谢手术袖状胃切除术作为肥胖和2型糖尿病患者治疗的方法之一,已经逐渐被医生和患者所认可。其手术操作相对简单,而手术效果不亚于胃旁路手术。原有的假说并不能完全解释袖状胃切除术减重降糖的机制。研究方法:构建肥胖糖尿病大鼠模型,随机分为袖状胃切除术组(SG组,n=10)和假手术组(S组,n=10),并进行相应手术。观察其体重变化情况;行OGTT试验,检测其术前术后的血糖和胰岛素的结果;用食物称重法和美兰灌胃法分别检测术前术后胃排空率和肠道传输率;用RT-PCR法检测胃肠道起搏细胞ICC的特异性标记物c-kit mRNA和SCF mRNA转录水平;用ELISA法检测术后两组间GLP-1分泌曲线;用免疫组化法检测术后两组胃肠道L细胞变化情况;用RT-PCR检测胃肠道GLP-1受体mRNA转录水平。研究结果:两组大鼠术前的体重差异没有统计学意义,SG组术后的体重显著低于假手术组(S组)P≤0.001;术后SG组大鼠血糖较术前明显降低,较术后S组血糖亦明显降低,且差异有统计学意义。SG组和S组术后12周的半小时进食量(g)分别为3.70±0.25和4.11±0.56(P=0.049),即SG组术后大鼠进食量小于S组;半小时胃排空率分别为62.8%±9.0%和52.1%±8.5%(P=0.013),即SG术后胃半小时排空比S组增快。肠道传输:SG组和S组术后12周的半小时肠道传输率分别为44.5%±3.7%和35.9%±6.2%(P=0.001),SG术后肠道传输速度比假手术组快。RT-PCR结果:不能认为两组大鼠术后胃窦组织的c-kit mRNA、SCF mRNA转录水平差异有统计学意义,两组大鼠的空肠和回肠组织c-kit mRNA、SCF mRNA转录水平差异有统计学意义,SG组大鼠的ckit mRNA、SCF mRNA转录水平较S组增高;术后SG组大鼠的GLP-1分泌均显著高于S组。SG组和S组大鼠空肠组织L细胞免疫组化切片平均光密度(MOD)分别为0.15±0.13和0.13±0.15(P=0.011);回肠组织L细胞免疫组化切片MOD分别为0.19±0.01和0.18±0.12(P=0.005);SG组大鼠术后空肠及回肠L细胞数量显著高于S组。研究结论:(1)肥胖糖尿病大鼠行袖状胃切除术后,出现明显的减重和降糖效果;(2)袖状胃切除术后,胃排空增快主要由胃容积减少引起,而小肠蠕动增快可能与ICC细胞增殖有关;(3)袖状胃切除术后,肠道L细胞及GLP-1R数量增加,肠道蠕动增快使得更多未消化的食糜更好地与L细胞和GLP-1R接触刺激L细胞分泌GLP-1,餐后GLP-1分泌高峰与食糜开始接触末端空肠和回肠的时间吻合;(4)随着GLP-1分泌增加及高峰提前,胰岛素的分泌高峰也相应出现提前,提示SG术后餐后胰岛素分泌及血糖的降低与GLP-1有关;(5)SG组术后空腹胰岛素的分泌比S组少,而对应的血糖同样降低,提示SG术后通过改善糖尿病的胰岛素抵抗降低血糖,而非刺激胰岛素分泌增多。
[Abstract]:Background: obesity and type 2 diabetes have become the major medical and health problems in China and the world. New metabolic surgery cuff gastrectomy as a treatment for obesity and type 2 diabetes has been gradually recognized by doctors and patients. Its operation is relatively simple, and the effect of operation is no less than gastric bypass surgery. The original hypothesis does not fully explain the mechanism of weight loss and glucose reduction in cuff gastrectomy. Methods: the obese diabetic rats were randomly divided into two groups: group SG (group SG) and group S (group S). The changes of body weight were observed, the results of blood glucose and insulin were detected by OGTT test, the gastric emptying rate and intestinal transmission rate were measured by food weighing method and methylene blue gavage method, respectively. The transcription levels of c-kit mRNA and SCF mRNA in gastrointestinal pacemaker cells were detected by RT-PCR, GLP-1 secretion curves were detected by Elisa, the changes of L-cells in gastrointestinal tract were detected by immunohistochemistry. The transcription level of GLP-1 receptor mRNA in gastrointestinal tract was detected by RT-PCR. Results: there was no significant difference in preoperative body weight between the two groups. The body weight in SG group was significantly lower than that in sham operation group (S group) P 鈮，

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