人参皂苷Rg1对糖尿病肾病大鼠肾保护作用的分子机制探讨

Discussion on Molecular Mechanism of Protection Effect of Ginsenoside Rg1on Kidneys of Rats with Diabetic Nephropathy

目的:观察人参皂苷Rg1对糖尿病肾病(DN)大鼠的肾脏保护作用,并探讨其作用机制。方法:60只雄性SD大鼠随机分为3组,正常组、模型组和Rg1干预组,大鼠采用高脂饮食联合STZ(50 mg/kg)腹腔注射建立糖尿病肾病(DN)大鼠模型。Rg1干预组大鼠给予人参皂苷Rg1(50 mg/kg·d^(-1))灌胃,同时正常组、模型组组大鼠予以相同体积生理盐水灌胃,分别在6周和12周时处死大鼠各半,收集血清和肾脏组织。分别采用ELISA、RT-q PCR和Western blot等方法进行相关指标检测。结果:与正常组比较,模型组组大鼠血清BUN、SCr、Cys C、RBP、MDA、TNF-α、IL-6和IL-1β含量升高(P<0.05),Rg1干预6周后,上述指标下降(P<0.05);模型组血清SOD、GSH活性降低,Rg1干预6周后两者活性升高(P<0.05);模型组肾组织Bcl-2mRNA和蛋白表达降低,Rg1干预6周后明显增强(P<0.05);模型组肾组织Bax和Caspase-3的mRNA和蛋白表达水平较正常组增强,Rg1干预6周后明显减弱(P<0.05)。干预12周后,上述指标进一步改善。结论:人参皂苷Rg1可以通过增强抗氧化能力,减轻炎症反应及抗细胞凋亡等缓解DN进程。

Objective： To observe the protection effect of Ginsenoside Rgl on kidneys of diabetic nephropathy rats, and discuss its molecular mechanism of alleviating diabetic nephropathy through inhibiting the apoptosis. Methods： 60 male SD rats were divided into three groups randomly. The rats of DN were induced with high fat diet accompanied with STZ solution （50 mg/kg） by intraperitoneal injection , after the establishment of DN rats model, the rats of Rglgroup were ig ginsenoside Rgl （50 mg , kg^-1 · d^-1 ） , while the rats of DN group and control group were given normal saline with the same volume respectively once a day, all of the rats were killed after 6 or 12 weeks, the serums and kidney tissues were collected. The related indexes were determined by ELISA, RT - qPCR and Western blot respectively. Results： Compared with the control group, the concentra- tions of serum BUN, SCr, CysC, RBP, MDA,TNF - α,IL -6 and IL - 1β of DN group rats were up - regulated, and those were down - regulated obviously after Rgl treatment for 6 weeks （ P 〈 0. 05 ） , the serum GSH and SOD activities of DN group rats were decreased, and they were increased after Rgl treatment for 6 weeks （ P 〈 0. 05 ） ; Compared with the control group, the expression levels of mRNA and protein of Bcl - 2 in the kidney tis- sues of DN group were lowered （ P 〈 0. 05 ） , they were raised significantly after Rgl treatment for 6 weeks ; and a inverse trend with Bax and Caspase -3. Morever, after Rgl treatment for 12 weeks, the improve effects above became more obvious. Conclusion： Ginsenoside Rgl has a capacity to alliviate kidney injury of the diabetes mellitus rats by enhancing the antioxidative ability, suppressing inflammatory and apoptosis.