血管紧张素Ⅱ受体阻断剂对糖尿病大鼠心肌内皮细胞向间充质转化的影响

Institute of Nephrology, Zhong da Hospital, Southeast University, Nanjing, China

Background: Emerging evidence has indicated that the endothelial-to- mesenchymal transition (EndMT) is a crucial event during early stages of cardiac fibrosis. In the present study, we first investigated the influence of Irbesartan (Irb) on myocardial EndMT in diabetic rats. Methods: Diabetic rats were divided into two groups: the diabetic group (DM) and the Irb-treated group (DM + Irb). Wistar-Kyoto rats served as controls. The pathological changes were investigated by microscopy. Immunofluorescence was performed to evaluate the co-expression of CD31 and fibroblast-specific protein 1 (FSP1). FSP1 and α-SMA expressions were detected by RT-PCR and Western blot analysis. EndMT was also studied in human aortic endothelial cells (HAECs) that had been exposed to high glucose (HG) levels. Results: Increased interstitial fibrosis was detected in the DM group. Double labeling revealed CD31 expression in FSP1-positive cells in the DM group, and this expression was diminished by Irb treatment (P < 0.05). In vitro, we found that HG stimulated angiotensin II synthesis in HAECs. When HAECs were exposed to HG, some of the cells acquired a spindle-shaped morphology and demonstrated a loss of CD31 labeling, which was attenuated by Irb treatment. FSP1 and α-SMA mRNA and protein expression levels were markedly upregulated in diabetic rats compared to controls, and their expressions were inhibited by Irb treatment (P < 0.05). Conclusion: The results provide the novel insight that an angiotensin II receptor blocker might prevent diabetic cardiomyopathy by abrogating EndMT in diabetic rats. © 2011 Elsevier Ireland Ltd.

Liu, B.-C.; Institute of Nephrology, Zhong da Hospital, Southeast University, Nanjing, China; email:liubc64@yahoo.com.cn