人参皂苷Rg1调节氧化应激和炎症因子表达改善糖尿病大鼠周围神经损伤

Ginsenoside Rg1 attenuates diabetic peripheral neuropathy in rats via antioxidant and anti-inflammatory mechanisms

目的:探讨人参皂苷Rg1(G-Rg1)对糖尿病周围神经病变(DPN)的保护作用及其机制。方法:雄性成年SD大鼠一次性腹腔注射STZ(40 mg/kg),两周后确认糖尿病造模成功。糖尿病大鼠随机分为模型组、G-Rg1小剂量组(10mg/kg)和G-Rg1大剂量组(30 mg/kg),1次/d,连续给药8周。8周后检测坐骨神经运动传导速度(MNCV)和感觉传导速度(SNCV),电镜观察其超微结构变化。ELISA法测定血清中TNF-α和IL-6水平及坐骨神经ROS和MDA水平,qPCR法检测坐骨神经TNF-α和IL-6的mRNA表达,Western blot检测坐骨神经中Nrf2、HO-1和NF-κB总蛋白表达。结果:DPN大鼠坐骨神经MNCV和SNCV降低(P<0.05),而G-Rg1可明显逆转这些现象(P<0.05);糖尿病模型组大鼠坐骨神经纤维出现质膜分离,电子密度不均等超微结构变化,而G-Rg1改善DPN大鼠坐骨神经超微结构变化。模型组大鼠血清TNF-α和IL-6水平明显升高(P<0.05),但G-Rg1抑制血清中TNF-α和IL-6水平(P<0.05)。模型组大鼠坐骨神经组织中MDA、ROS及血清中TNF-α、IL-6 mRNA水平明显升高,而G-Rg1显著抑制坐骨神经组织ROS、MDA及血清中TNF-α、IL-6 mRNA水平(P<0.05)。模型组Nrf2和HO-1蛋白表达明显降低而NF-κB蛋白表达明显升高,而G-Rg1增加Nrf2和HO-1表达,降低NF-κB蛋白表达(P<0.05)。结论:G-Rg1通过调节糖尿病大鼠坐骨神经氧化应激和炎症因子表达保护神经损伤。

Objective:To evaluate the effect of Ginsenoside Rg1(G-Rg1)on diabetic peripheral neuropathy(DPN)in rats and probe its relevant mechanisms.Methods:Adult SD rats were received a single dose of STZ(40 mg/kg),and 2 weeks later were checked for the establishment of diabetes mellitus.Diabetic rats were divided into diabetic model group,low-dose G-Rg1(10 mg/kg)group and high-dose G-Rg1 group(30 mg/kg),and G-Rg1 was intragastrically given once a day for 8 weeks.Then,both the motor nerve conduction velocity(MNCV)and the sensory nerve conduction velocity(SNCV)of the sciatic nerve in rats were measured,and microstructural(under an electromicroscope)changes of the sciatic nerve were observed.Concentrations of TNF-αand IL-6 in plasma and levels of reactive oxygen species(ROS)and malondialchehyche(MDA)in sciatic nerve tissues were analyzed by ELISA assay.mRNA expressions of TNF-αand IL-6 were evaluated by qPCR,meanwhile,protein expressions of Nrf2,HO-1 and NF-κB were determined by Western blot in sciatic tissues.Results:There was decreased MNCV and SNCVin DNP rats(P<0.05),whereas G-Rg1 can significantly reverse this phenomenon(P<0.05);G-Rg1 also improved abnormal microstructural changes in sciatic nerve of diabetic rats such as plasma membrane separation and electron density irregularity.There was a significant elevation of plasma TNF-α(P<0.05)and IL-6(P<0.05)concentrations that was inhibited by G-Rg1(TNF-α:P<0.05,IL-6:P<0.05);additionally,there were significant increases in production of ROS(P<0.05)and MDA(P<0.05)and gene expressions of TNF-α(P<0.05)and IL-6(P<0.05)in sciatic nerve tissues in diabetic rats,which were prevented by G-Rg1(P<0.05 for all).Moreover,the protein expressions of Nrf2(P<0.05)and HO-1(P<0.05)were decreased,while the protein expression of NF-κB(P<0.05)was increased in the sciatic nerve of diabetic rats,but G-Rg1 respectively enhanced the Nrf2(P<0.05)and HO-1(P<0.05)protein expressions and decreased the NF-κB protein level(P<0.05 for all).Conclusion:G-Rg1 has protective effects on sciatic nerve damage in diabetic rats,which may be mediated via its anti-oxidant and anti-inflammatory actions.