奥美沙坦保护糖尿病db／db小鼠肾脏的研究

The study of the renoprotective effects of olmesartan in diabetic db/db mice

目的探讨奥美沙坦对db/db小鼠ACE2-Ang-(1-7)-MasR受体轴的影响。方法将8周龄db/db小鼠(血糖>16.7mmol/L)随机分为对照组(n=12)和奥美沙坦组(n=12)。无创血压仪监测小鼠血压;收集24 h尿液检测尿白蛋白/肌酐指标,酶联免疫吸附实验(ELISA)检测血管紧张素Ⅱ和尿8-羟基脱氧鸟苷(尿8-OHdG)水平;PAS和Masson染色方法观察肾脏病理情况;Western blot检测肾脏组织AT-1R、ACE2、Ang-(1-7)-Mas R、P22-phox、P47-phox和p-Erk1/2的蛋白表达。结果与对应时间点的对照组相比,奥美沙坦组血压无明显变化,24 h尿蛋白、尿肌酐和尿8-OHdG水平降低,血管紧张素Ⅱ(Ang-Ⅱ)水平下降;肾脏病理改善;ACE2、Ang-(1-7)-MasR、p-PI3K和p-AKT的蛋白表达明显上调,AT-1R、P22-phox、P47-phox和p-Erk1/2的蛋白表达明显下调(均P<0.05)。结论奥美沙坦对糖尿病肾脏有保护作用,其机制与调节ACE2-Ang(1-7)-Mas受体轴减轻氧化应激有密切关系。

Objective To explore the effect of olmesartan in db/db mice via modulation of ACE2-Ang （1-7） -Mas receptor axis. Methods 8-week db/db mice （6 h fasting plasma glucose 〉 16.7 mmol/L） were allocated randomly into the control group （n= 12） and the olmesartan group （n = 12）. The level of blood pressure was measured by non-invasive blood pressure instrument. The level of 24 h proteinuria/urine creatinine was measured by routine chemical method. The level of serum Ang-II and urinary 8-OHdG were measured with ELISA. The renal pathological changes were examined by the methods ofPAS, Masson. The expressions of AT-1R, ACE2, Ang- （1-7） -Mas R, P22-phox, P47-phox and p-Erk1/2 were detected by Western blot. Results There was no difference in the level of blood pressure. However, compared with the control group, the expression of ACE2, Ang- （1-7） -Mas R protein and the level of insulin were increased significantly in olmesartan group. Meanwhile, the level of urinary 8-OHdG, the expression of AT-1R, P22-phox, P47-phox, p-Erk1/2 and the other indexes were decreased obviously （P〈0.05）. Conclusion Olmesartan protects the kidney in diabetes via modulation of ACE2-Ang- （1-7） -Mas receptor axis, thus reduces kidney oxidative stress.