The Influence of Ang Ⅱ Receptor Blocker on the Pancreatic Islet Function and Fibrosis in Diabetic Rats and Its Mechanism

He Junhua; Wu Huilu; Wang Li; Dan Ni; Guo Hong; Li Xing

doi:10.3969/j.issn.1672-1349.2018.01.010

Abstract：Objective To investigate the effects and mechanism of the type 1 receptor blocker of Ang Ⅱ (Iosartan) on pancreatic islet function and fibrosis in rat model of streptozotocin (STZ)-induced diabetes mellitus (DM).Methods Twenty-six male wistar rats were randomly divided into 3 groups:normal control group fed by standard laboratory diet,DM control group fed by high-fat diet and injected with STZ,and Iosartan group receiving injection of STZ followed by Losartan treatment.Body weight,blood glucose levels,fasting serum insulin levels,and homeostasis model assessment of insulin resistance (HOMA-IR) were measured.The pancreas was collected for histological examination.The levels of transforming growth factor (TGF)-β1,Smad 7 and collagen I protein and gene expression in pancreatic tissue were measured by immunohistochemistry and real time polymerase chain reaction (PCR).Results Compared to normal control group,body weight and serum insulin levels were significantly decreased,blood glucose and HOMA-IR significantly increased in DM control group (all P ＜0.05).Compared to DM control group,there were significant improvements in every index except body weight in Iosartan group (all P ＜0.05).Hemalum-Eosin (HE) staining analysis showed that pancreatic β cells in DM control group were irregularly arranged,and pancreatic fiber tissues increased in amount.In contrast,the lesion of islet tissue in Iosartan group was alleviated,but not restored to the normal level.The expressions of TGF-β1 and collagen Ⅰ protein and mRNA were increased,Smad 7 decreased in DM control group compared to normal control group.The DM-associated elevation of TGF-β1 and collagen Ⅰ and reduction of Smad7 were significantly reversed in Iosartan group (all P ＜0.05).Conclusion Losartan can improve pancreatic islet function and alleviate islet fibrosis,which may be related to TGF-β1 down-regulation and Smad 7 up-regulation that reduce the level of collagen Ⅰ through signal transduction pathway of TGF-β1/Smads.