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

Zhouluotong capsule inhibits oxidative stress in diabetic perpheral ueuropathy mice by upregulating the activity of Nrf2

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 pe- ripheral 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-l）. C57BL/6 mice were elected as control group. Mice were given capsules intragastrically for 12 weeks. Mo- tor nerve conduction velocity （MNCV）, fasting blood- glucose （FBG） and glycosylated hemoglobin （ HbA1 c） were observed; Activity of superoxide dismutase （SOD）, glutathion peroxldase, glutathione peroxidase （ GSH-Px）, hydrogen peroxidase （CAT） and content of Malondialdehyde （MDA） in blood were detected by colorimetric method. The mRNA expression of Nrf2, heine oxygenase-1 （HO-1）,r-glutamyl eysteine syn-thetase （r-GCS） of sciatic nerve was examined by Re- al Time PCR. The protein expression of total Nrf2, in- tranuclear Nrf2, HO-1, r-GCS was examined by West- ern blot. Results ZLT could increase MNCV, activity of SOD, GSH-Px, CAT, and decrease FBG, I-IbAlc, MDA. Compared with the model group, the protein ex- pression 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 I-IO-1, r-GCS mRNA and protein increased in ZLT group. Conclusion ZLT can inhibit oxidative stress in DPN of mice via promoting the Nrf2 nuclear translocation.