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目的:探讨人参皂苷对波动性高血糖大鼠肾脏转录因子NF-E2相关因子2(NF-E2-related factor2,Nrf2)及醌氧化还原酶1(quinone oxidoreductase l,NQO1)表达的影响及其机制。方法:将48只雄性SD大鼠随机分成正常对照组(NC组,n=8)和糖尿病模型组(n=40)。高脂饲料喂养糖尿病模型组大鼠2周后用小剂量链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,之后随机分为稳定高糖组(SH组,n=8)和波动性高糖组(FH组,n=32),FH组错时注射葡萄糖、胰岛素制备血糖波动大鼠模型。2周后,将FH组随机分为4组,分别是低剂量组(LG组),中剂量组(MG组),高剂量组(HG组)及波动性高糖组(BG组),予人参皂苷低中高剂量(14、28、56mg/(kg·d))干预相对应的模型组8周。实验结束后切取肾脏组织,用western blot和RTPCR(Real-time Polymerase Chain Reaction)检测Nrf2和NQO1蛋白及mRNA表达。结果:与NC组相比,SH组Nrf2和NQO1的蛋白及mRNA的表达明显增加(P<0.05),与SH组相比,BG组Nrf2和NQO1的蛋白及mRNA的表达明显增加(P<0.05),与BG组相比,人参皂苷治疗组Nrf2和NQO1的蛋白及mRNA的表达明显增加(P<0.05)。结论:人参皂苷能够进一步促进波动性高糖状态下Nrf2及NQO1蛋白及mRNA表达,通过增加NQO1的含量,提高机体的抗氧化应激能力,保护波动性高血糖所致的肾脏损伤。
Objective: To investigate the effects of ginsenosides on the expression of renal transcription factors NF-E2 related factor 2 (Nrf2) and quinone oxidoreductase 1 (NQO1) in hyperglycemic rats and its mechanism . Methods: Forty eight male Sprague-Dawley rats were randomly divided into normal control group (NC group, n = 8) and diabetic model group (n = 40). Diabetic rats were fed with high-fat diet for 2 weeks and then were induced by low-dose streptozotocin (STZ) to establish diabetic rat model. The rats were randomly divided into stable high glucose group (SH group, n = 8) and high volatility Sugar group (FH group, n = 32). FH group was injected with glucose and insulin to prepare the rat model of blood glucose fluctuation. After 2 weeks, the FH group was randomly divided into 4 groups: low dose group (LG group), middle dose group (MG group), high dose group (HG group) and high glucose group (BG group) Ginsenoside low, medium and high doses (14, 28, 56 mg / (kg · d)) intervention for the model group for 8 weeks. At the end of the experiment, the kidney tissues were excised and the protein and mRNA expression of Nrf2 and NQO1 were detected by western blot and RTPCR (Real-time Polymerase Chain Reaction). Results: Compared with NC group, the protein and mRNA expression of Nrf2 and NQO1 in SH group were significantly increased (P <0.05), compared with SH group, the expression of Nrf2 and NQO1 protein and mRNA in BG group were significantly increased (P <0.05 ). Compared with BG group, the protein and mRNA expression of Nrf2 and NQO1 in Ginsenoside treatment group increased significantly (P <0.05). CONCLUSION: Ginsenosides can further promote the expression of Nrf2 and NQO1 protein and mRNA under high glucose and high volatility. By increasing the content of NQO1, ginsenosides can improve the body’s ability of anti-oxidative stress and protect renal damage caused by hyperglycemia.