艾塞那肽促进肥胖糖尿病大鼠胰腺组织的胆固醇流出

Exenatide promotes cholesterol efflux in pancreatic tissue of obese diabetic rats

目的利用肥胖糖尿病大鼠模型研究艾塞那肽对胰腺组织ABCA1表达及胆固醇代谢的影响。方法SD雄性大鼠48只,选取部分大鼠通过高脂饮食和STZ药物诱导建立肥胖合并2型糖尿病大鼠模型,所有大鼠分为4组:正常大鼠注射生理盐水组(A组,12只),正常大鼠注射艾塞那肽组(B组,12只),肥胖糖尿病大鼠注射生理盐水组(C组,9只),糖尿病模型大鼠艾塞那肽组(D组,9只),10周后通过real-time PCR、Western blot、油红“O”染色、组织胆固醇含量测定、HE染色等检测艾塞那肽对大鼠胰腺组织ABCA1表达、胆固醇代谢、胰岛功能的影响。结果通过real-time PCR、Western blot等发现较之SD大鼠,肥胖糖尿病大鼠胰腺组织ABCA1表达降低,油红“O”染色显示胰腺组织出现明显脂质沉积,组织胆固醇含量测定发现胰腺组织胆固醇含量增加,HE染色显示胰岛体积显著缩小,结构紊乱(P<0.05)。艾塞那肽可上调肥胖糖尿病大鼠胰腺组织ABCA1表达,减轻胰腺组织脂质沉积,降低胰腺组织胆固醇含量,胰岛数目、体积增多,排列更为规则(P<0.05)。结论糖脂毒性可导致大鼠胰腺组织ABCA1表达降低,胆固醇流出受阻,胰腺组织胆固醇蓄积。艾塞那肽可上调肥胖糖尿病大鼠胰腺组织ABCA1介导的胆固醇流出,明显降低胆固醇含量,改善胰岛功能。

Objective To study the effect of exenatide on the expression of ABCA1 and cholesterol metabolism in the pancreas of obese diabetic rats.Methods Twenty-four normal male SD rats and 18 obese diabetic rats(induced by high-fat feeding and STZ injection)were both divided equally into 2 groups for injections of saline or exenatide.After treatment for a week,the expression of ABCA1,cholesterol metabolism,and islet function of the rats were examined using real-time PCR,Western blotting,oil red O staining,cholesterol content determination,and HE staining.Results The expressions of ABCA1 at both mRNA and protein levels in pancreatic tissue were significantly lower in obese diabetic rats than in normal SD rats.The obese diabetic rats showed obvious lipid deposition and increased cholesterol content in the pancreatic tissue with significantly reduced islet volume and structural changes(P<0.05);exenatide treatment of the diabetic rats significantly up-regulated ABCA1 expression,reduced lipid deposition and cholesterol content in pancreatic tissue,and increased number and volume of the islets,which presented with more orderly alignment(P<0.05).Conclusion Obese diabetic rats have lowered ABCA1 expression,cholesterol efflux block,and cholesterol accumulation in the pancreatic tissue.Exenatide can up-regulate ABCA1 expression and promote cholesterol efflux to reduce cholesterol content in the pancreatic tissue and improve islet function in obese diabetic rats.