厄贝沙坦对糖尿病大鼠胰腺病变的影响及机制探讨

Effect and Mechanism of Irbesartan on Pancreatic Lesions in Diabetic Rats

目的 观察厄贝沙坦干预后糖尿病大鼠胰腺病变改善情况,探讨其可能的保护机制。方法 于2021年4—10月期间选取24只大鼠为研究对象,并随机分为正常对照组(NC)、2型糖尿病模型组(T2DM)、2型糖尿病模型+厄贝沙坦干预组(ARB),每组8只。比较3组大鼠的空腹血糖、空腹胰岛素、C肽、血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)mRNA水平、ACE2蛋白相对表达量、胰岛β细胞凋亡率以及胰岛β细胞超微结构改变情况。结果 与NC组比较,T2DM组空腹血糖升高,空腹胰岛素及C肽水平下降,ACEmRNA升高而ACE2mRNA及蛋白水平下降,胰岛β细胞凋亡率升高,差异有统计学意义(P<0.05);与T2DM组对比,ARB组空腹血糖下降,胰岛素及C肽水平上升,ACEmRNA降低而ACE2mRNA及蛋白水平升高,胰岛β细胞凋亡率下降,差异有统计学意义(P<0.05)。NC组胰岛β细胞的超微结构正常,T2DM组的胰岛β细胞的超微结构紊乱,ARB组的胰岛β细胞的超微结构改善。结论 胰腺局部ACE、ACE2表达失衡可能为糖尿病胰腺局部病变的机制之一,厄贝沙坦可以通过调节局部ACE、ACE2表达情况改善胰岛β细胞超微结构,减少胰岛β细胞凋亡。

Objective To observe the improvement of pancreatic lesions in diabetic rats after irbesartan intervention,and to explore its possible protective mechanism.Methods Total of 24 rats were selected from April to October 2021 and randomly divided into normal control group(NC),type 2 diabetes model group(T2DM)and Type 2 diabetes model+irbesartan intervention group(ARB),with 8 rats in each group.Fasting blood glucose,fasting insulin,Cpeptide,angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2)mRNA levels,relative expression of ACE2 protein,apoptosis rate of pancreaticβcells and ultrastructural changes of pancreaticβcells of rats in 3 groups were compared.Results Compared with NC group,fasting blood glucose increased,fasting insulin and Cpeptide levels decreased,ACEmRNA increased and ACE2mRNA and protein levels decreased in,the apoptosis rate of islet beta cells increased in T2DM group,the difference was statistically significant(P<0.05).Compared with T2DM group,fasting blood glucose decreased,insulin and C-peptide levels increased,ACEmRNA decreased and ACE2mRNA and protein levels increased,the apoptosis rate of islet beta cells decreased in ARB group,the difference was statistically significant(P<0.05).The ultrastructure of islet beta cells in NC group was normal,that in T2DM group was disordered,and that in ARB group was improved.Conclusion The imbalance of local ACE and ACE2 expression in pancreas may be one of the mechanisms of diabetic pancreatic local lesions.Irbesartan can improve the ultrastructure of pancreatic β cells and reduce the apoptosis of pancreatic β cells by regulating local ACE and ACE2 expression.