糖尿病大鼠胰腺血管紧张素受体Mas表达降低

 目的 糖尿病大鼠观察胰腺血管紧张素受体Mas在糖尿病发病机制中的可能作用。方法 选48周龄的雄性OLETF大鼠及年龄和性别匹配的同品系LETO大鼠行口服糖耐量试验。氧化酶法测定血糖，ELISA法测定血清胰岛素，血浆生化仪测定血清甘油三酯及总胆固醇。免疫组化检测Mas及血管紧张素转换酶2（ACE2）在胰腺的表达。应用淋巴细胞分离液分离胰岛细胞，QRT-PCR方法检测胰岛细胞Mas及ACE2的mRNA表达，Western印迹法测定大鼠胰岛细胞Mas及ACE2的蛋白表达。结果 OLETF大鼠的体重、甘油三脂、总胆固醇、空腹血糖及服糖后2h血糖、空腹胰岛素水平较LETO大鼠均显著升高（P<0.05～0.01）。Mas及ACE2在胰腺的内、外分泌腺均有表达。OLETF糖尿病大鼠其胰岛细胞Mas的mRNA及蛋白表达均明显低于LETO对照组（P<0.05），两组间ACE2的mRNA及蛋白水平无显著差异。结论 糖尿病发生过程中胰腺Mas mRNA及蛋白水平的下降先于ACE2出现。Mas在胰腺的表达可能成为治疗胰腺疾病的靶点之一。

Down expression of angiotensin receptor-Mas receptor in rat pancreas with diabetes

Objective Using the diabetic animal model, we aimed to investigate the putative role of angiotensin receptor─Mas receptor in diabetes pathogenesis. Methods Oral glucose tolerance test (OGTT) was performed in age-matched LETO and Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 48 weeks. The following items including blood glucose, serum insulin, serum levels of total cholesterol and triglyceride were determined in all rats. Detection of the expression of Mas and ACE2 proteins in rat pancreas using immunohistochemistry. Pancreas were procured from rats. After the digestion phrase, the islets were purified by Lymphoprep. The protein levels of Mas and ACE2 from the rats’ islets were detected by Western blotting analysis. In addition, Mas and ACE2 mRNA levels were measured by real-time PCR. Results The body weight, serum levels of total cholesterol and triglyceride, fasting blood glucose, OGTT2h blood glucose and fasting insulin levels in OLETF rats were all significantly higher than those in LETO controls (P<0.05～0.01). Mas protein and ACE2 protein were detected in both endocrine tissue and exocrine tissue of pancreas. Compared with LETO controls, the mRNA and protein levels of Mas in islets of OLETF rats showed down-regulated (P<0.05). Conclusion During the development of diabetes, the changes of Mas in rat pancreas islets were detected earlier than ACE2.These findings might be an important therapeutic target in pancreatic disease.