2型糖尿病大鼠胃旁路术后胰高血糖素样肽-1及其受体在胰腺表达的变化

Changes of glucagon-like peptide-1 in plasma and glucagon-like peptide-1 receptor in pancreas after gastric bypass in rats with type 2 diabetes mellitus

目的 观察胃旁路术（GBP）后2型糖尿病大鼠（GK大鼠）胰高血糖素样肽-1（GLP-1）及其受体在胰腺组织中的表达变化,探讨GBP治疗2型糖尿病机制.方法 将30只8周龄雄性GK大鼠随机分为手术组（10只）、假手术组（10只）、饮食配对组（10只）,另8周龄雄性SD作为空白对照组（10只）.检测和比较术前及术后1、2、4周各组大鼠空腹血糖（FPG）、GLP-1水平.术后4周处死大鼠,取胰腺组织行苏木素-伊红（HE）染色,光镜下观察各组胰岛大体形态学改变,免疫组织化学法检测胰高血糖素样肽-1受体（GLP-1 R）的变化.结果 手术组术后各时间点FPG水平[（11.06±0.52）、（7.49±0.34）、（5.20 ±0.08） mmol/L]均低于术前（P＜0.05）;GLP-1[（12.11±0.40）、（13.64 ±0.23）、（26.40±0.39） pmol/L]明显升高（P＜0.01）;HE染色胰岛逐渐饱满,胰腺组织中GLP-1R表达明显增多.结论 GBP降糖效果确切,GLP-1及其受体的上调是血糖调控的重要机制之一.

Objective To investigate the changes of glucagon-like peptide-1 （GLP-1） in plasma and GLP-1 receptor （GLP-1 R） in pancreas after gastric bypass in rats with type 2 diabetes mellitus （GK rats） and to discuss the antidiabetic mechanisms.Methods Thirty male GK rats aged 8 weeks were randomly divided into 3 groups：the operation group （n =10）,the sham operation group （n =10） and the diet pairing group （n =10）,and 10 male SD rats aged 8 weeks served as blank control group （n =10）.The levels of fasting blood glucose （FPG） and GLP-1 were measured and compared among the 4 groups at 1st,2nd and 4th week after the operation,and then the rats were decapitated to retrieve the pancreas to hematoxylin and eosin （HE） staining.Histomorphological changes including single islet area and pancreas islet number in each group were observed after HE staining under light microscopy,and the changes of GLP-1R expression were measured by immunohistochemistry.Results In GK operation group,the FPG levels [（11.06 ±0.52）,（7.49 ±0.34）,and （5.20 ±0.08） mmol/L] were decreased to the normal from the 1 st week after the operation （P 〈 0.05）,and the GLP-1 levels [（12.11 ± 0.40）,（13.64 ± 0.23）,and （26.40 ± 0.39） pmol/L] increased significantly （P 〈0.01）.The size of single pancreas islet and the amount of pancreas islets were increased significantly,and the expression of GLP-1R in the pancreas was significantly higher in GK operation group.Conclusion Gastric bypass surgery can significantly reduce the blood glucose level.The up-regulation of GLP-1 and GLP-1R expression was one of the important mechanisms regulating blood glucose.