周络通胶囊激活转录因子Nrf2抑制糖尿病周围神经病变小鼠氧化应激

摘要

目的 观察周络通胶囊激活转录因子NF-E2相关因子2(Nrf2)对糖尿病周围神经病变小鼠氧化应激的影响.方法 KK/Upj-Ay小鼠随机分为模型组、周络通胶囊高、中、低剂量组,另设C57BL/6小鼠对照组.灌胃给药12周,测定坐骨神经传导速度(MNCV)、空腹血糖(FBG)及糖化血红蛋白(HbA1c);比色法测定血液中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)、过氧化氢酶(CAT)含量;荧光定量PCR测定坐骨神经Nrf2、血红素氧合酶-1(HO-1)、γ-谷氨酰半胱氨酸合成酶(γ-GCS)mRNA的表达;Western blot测定坐骨神经总Nrf2、核内Nrf、HO-1、γ-GCS蛋白的表达.结果 周络通能明显提高MNCV、SOD、GSH-Px、CAT,降低FBG、HbA1c、MDA;周络通组核内Nrf2蛋白表达明显上升;Nrf2 mRNA和总Nrf2蛋白表达在各组无差异;能升高HO-1、γ-GCS mRNA和蛋白表达.结论 周络通胶囊通过促进Nrf2核转位发挥其抗DPN小鼠氧化应激损伤的作用.%Aim To investigate the effects of Zhouluo-tong capsule ( ZLT ) on oxidative stress in diabetic peripheral neuropathy mice by upregulating the activity of nuclear factor E2-related factor 2 ( Nrf2 ). Methods KK/Upj-Ay mice were randomly divided into model and ZLT groups (6.85, 3.43, 1. 71 g·kg-1 ). C57BL/6 mice were elected as control group. Mice were given capsules intragastrically for 12 weeks. Motor nerve conduction velocity ( MNCV ), fasting blood-glucose ( FBG ) and glycosylated hemoglobin ( HbA1c ) were observed. Activity of superoxide dismutase ( SOD ), glutathion peroxidase, glutathione peroxidase ( GSH-Px ), hydrogen peroxidase ( CAT ) and content of Malondialdehyde ( MDA ) in blood were detected by colorimetric method. The mRNA expression of Nrf2, heme oxygenase-1 ( HO-1 ), γ-glutamyl cysteine synthetase ( γ-GCS ) of sciatic nerve was examined by Real Time PCR. The protein expression of total Nrf2, intranuclear Nrf2, HO-1, γ-GCS was examined by Western blot. Results ZLT could increase MNCV, activity of SOD, GSH-Px, CAT, and decrease FBG, HbAlc, MDA. Compared with the model group, the protein expression of intranuclear Nrf2 increased in ZLT group. The expression of Nrf2 mRNA and total Nrf2 showed no difference in each group. Compared with the model group, the expression of HO-1, γ-GCS mRNA and protein increased in ZLT group. Conclusion ZLT can inhibit oxidative stress in DPN of mice via promoting the Nrf2 nuclear translocation.u0000d to