贝母素乙对糖尿病肾病大鼠肾功能保护的作用机制

Protection Effect of Peiminine on Renal Function in Rats with Diabet-ic Nephropathy

目的探究贝母素乙对糖尿病肾病大鼠肾功能及组织病变的保护的作用机制.方法体外培养大鼠肾小球系膜细胞(hbzy-1),并分为空白对照组、高糖组、低浓度贝母素乙组、中浓度贝母素乙组、高浓度贝母素乙组,检测hbzy-1存活率、凋亡率、凋亡相关蛋白及PI3K、 FOXO3信号通路相关蛋白表达,检测丙二醛、超氧化物歧化酶、活性氧和谷胱甘肽过氧化物酶含量;添加AKT抑制剂后再次检测上述指标变化.制作糖尿病肾病大鼠模型,检测尿液中蛋白尿;血清肌酸酐,尿素氮的水平,并观察组织病理损伤.结果随着贝母素乙处理浓度升高,肾小球系膜细胞凋亡率、凋亡蛋白表达、 FOXO3蛋白表达及氧化应激水平显著受到抑制, PI3K 磷酸化受到促进( P <0. 05),且呈浓度依赖性.结论贝母素乙可以通过FOXO3通路降低肾小球系膜细胞氧化应激反应保护糖尿病肾病大鼠肾功能,且呈浓度依赖性.

Objective To explore the protection effect of peiminine on renal function and his-topathological changes in rats with diabetic nephropathy. Methods Rat mesangial cells ( HBZY-1) were cultured in vitro and divided into blank control group, high-glucose group, low-concentration peiminine group, medium-concentration peiminine group and high-concentration peiminine group. The HBZY-1 survival rate, apoptosis rate, expression levels of apoptosis-related proteins and signaling pathway-related proteins p-PI3K and P-AKT were detected. The contents of malondialde-hyde, superoxide dismutase, reactive oxygen species and glutathione peroxidase were detected. A rat model of diabetic nephropathy was established, and the protein in urine and serum creatinine and urea nitrogen were detected. The histopathological damage was observed. Results With the in-crease of the concentration of peiminine, the apoptotic rate of rat mesangial cells, expression of ap-optosis-related proteins, Foxo3 protein expression and oxidative stress level were significantly inhibi-ted, and the phosphorylation of PI3K was significantly promoted ( P <0. 05) in a concentration-dependent manner. Conclusion Peiminine can reduce oxidative stress reactions in mesangial cells and protect renal function in rats with diabetic nephropathy through Foxo3 pathway in a concentra-tion-dependent manner.