人参皂苷对波动性高血糖大鼠肾脏Nrf2/ARE信号通路的影响

Effect of ginsenoside on Nrf2/ARE signaling pathway in the kidney of rats exposed to intermittent high glucose

关键词:  人参皂苷  Nrf2/ARE信号通路  波动性高血糖  血红素加氧酶-1  γ-谷氨酰半胱氨酸合成酶

Key words:  ginsenoside  nuclear factor erythroid-2-related factor-2 signaling pathway  fluctuating hyperglycemia  heme oxygenase-1  γ-glutamylcysteine synthethase

摘要:

[目的] 探讨人参皂苷对波动性高血糖大鼠肾脏氧化应激及转录因子NF-E2相关因子2（Nrf2）/应答元件（ARE）信号通路的影响。[方法] 实验以32只雄性SD大鼠为研究对象，分为正常对照组（NC组，n=8只）和波动性高糖模型组（n=24只），高脂饲料喂养模型组2周后，链脲佐菌素（STZ）35 mg/kg腹腔注射诱导建立糖尿病大鼠模型，错时注射葡萄糖和胰岛素，建立血糖波动组模型，2周后，将波动性高糖模型组随机分为3组，分别为波动性高血糖组（FHG组，n=8），人参皂苷低剂量组（LG组，n=8），人参皂苷高剂量组（HG组，n＝8）。予人参皂苷低高剂量[14、56 mg/（kg·d）]干预相对应的模型组8周后，切取肾脏组织，用蛋白免疫切迹方法（Western blot）和实时荧光定量聚合酶链式反应（RT-PCR）检测血红素加氧酶-1（HO-1）、Nrf2、γ-谷氨酰半胱氨酸合成酶（γ-GCS）蛋白及mRNA表达。[结果] 与NC组相比，FHG组Nrf2的蛋白及mRNA的表达明显增加（P<0.05），而HO-1、γ-GCS的表达明显降低（P<0.05）；但人参皂苷治疗后，LG组及HG组HO-1、γ-GCS、和Nrf2蛋白及mRNA表达明显增高（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下游HO-1、γ-GCS蛋白及mRNA表达，增加抗氧化蛋白的含量，提高机体的抗氧化应激能力，对波动性高糖所致的肾脏损伤有一定的保护作用。

Abstract:

[Objective] To observe the effects of ginsenside on Nrf2/ARE signaling pathway in the kidney of diabetic rats exposed to intermittent high glucose.[Methods] Thirty-two male SD rats were randomly divided into normal group (group NC,n=8) and fluctuating hyperglycemia model group (n=24).The fluctuating hyperglycemia model group established by injection of a small dose of streptozotoein (STZ) after feeding them with high-fat diet for 2 weeks,and by alternative intraperitoneal injection of insulin and glucose.Then they were randomly divided into three groups of FHG (the fluctuating hyperglycemia group),LG (treated with ginseng 14 mg/(kg·d),HG[treated with ginseng 56 mg/(kg·d)].After 8 weeks HO-1,γ-GCS and NRF2 protein were observed by western blot and HO-1,γ-GCS,NRF2 mRNA were measured by RT-PCR.[Results] Compared with group NC,levels of NRF2 protein and mRNA in FHG groups were significantly decreased (P<0.05),levels of HO-1,γ-GCS,NRF2 protein and mRNA in FHG groups were significantly increased (P<0.05);compared with group FHG,levels of HO-1,γ-GCSand NRF2 protein and mRNA in group LG and HG were significantly increased (P<0.05).[Conclusion] Ginsenoside could further promote the expression of HO-1,γ-GCS,protein and mRNA in the downstream gene of Nrf2 in the state of intermittent high glucose.Ginsenoside reduce the production of reactive oxygen species and improve the body's ability to restrain oxidative stress,which has a protective effect on the rat renal injury induced by glucose fluctuation.