不同降糖药物对2型糖尿病大鼠胰岛β细胞凋亡及再生作用的影响

摘要

目的 观察不同降糖药物对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠胰岛β细胞凋亡与再生作用的影响.方法 将SD大鼠随机分为正常对照组、T2DM未治疗组、利拉鲁肽组、西格列汀组、罗格列酮组各20只.正常对照组给予普通饲料,其余各组给予高脂饲料喂养8周后以链脲佐菌素30 mg/kg腹腔注射,成模后分别给予上述三药治疗4周.其余2组给予等量生理盐水皮下注射.于治疗前后分别取大鼠血清,以苏木精-伊红染色观察胰岛细胞组织学改变,以原位末端标记法检测胰岛β细胞凋亡,以实时荧光定量逆转录-聚合酶链反应法检测胰岛细胞胰腺十二指肠同源盒-1(pancreatic duodenal homeobox-1,PDX-1)基因的表达.结果 利拉鲁肽组、罗格列酮组及西格列汀组治疗后空腹血糖较T2DM组及治疗前均明显降低(P＜0.05).胰岛结构及胰岛细胞数量均明显好于未治疗组,胰岛β细胞凋亡率明显降低(P＜0.05).结论 利拉鲁肽、罗格列酮及西格列汀均可改善T2DM大鼠血糖,利拉鲁肽对减少体质量优丁西格列汀及罗格列酮,3种药物均可增加胰岛β细胞数量、减少p细胞凋亡,其机制可能与增加胰岛β细胞PDX-1基因的表达有关,以利拉鲁肽作用更优.%Objective To observe the role of different drugs on proliferation and regeneration of islet beta cells in type 2 diabetes mellitus(T2DM) rats.Methods Sprague-Dawley rats were randomly divided into normal control group,T2DM group,liraglutide group,sitagliptin group and rosiglitazone group,20 in each group.Normal control group was given normal diet and the other experimental groups were given high fat diet.After eight weeks,the high fat diet group was intraperitoneally injected with streptozotocin 30 mg/kg,and the liraglutide group,the sitagliptin group and the rosiglitazone group were treated for 4 successive weeks.The other groups were treated with normal saline by subcutaneous injection.The blood sample was collected before and after 4 weeks of treatment.Hematoxylin-eosin staining was used to observe the islet cell histology change.TdT-mediated dUTP nick end labeling was used to detect apoptosis of islet cells.Real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to detect the expression of pancreatic duodenal homeobox-1 (PDX-1) gene in rat pancreatic islet cells.Results After treatment,compared with the T2DM group and that before treatmemt,the level of fasting blood glucose in the liraglutide group,sitagliptin group and rosiglitazone group was distinctly lower(P＜0.05),the structure and the number of islets were significantly better,the level of apoptosis rate was lower (P＜ 0.05).Conclusion Liraglutide,sitagliptin and rosiglitazone could significantly improve the glucose.The effect of liraglutide on decreasing the body weight was better than that of rosiglitazone and Sitagliptin.Liraglutide,sitagliptin and rosiglitazone could significantly increse the number of pancreatic islet beta cells and decrease the islet cell apoptosis rate,the effect may be associated with an increased expression of PDX-1 gene,the effect of liraglutide was better than that of rosiglitazone and Sitagliptin.