糖痹康对糖尿病大鼠坐骨神经Keap1/Nrf2信号的作用机制  

Mechanism of Tangbikang in Keap1/Nrf2 signal pathway of sciatic nerve of diabetic rats

作　　者：张岩[1] 穆晓红[1] 孙文[1] 吴丽丽[1] 秦灵灵[1] 樊怡欣[1] 郭璇[1] 许光远[1] 李伟笠 姜月滢 邓莉[2] 洪明昭 刘铜华[1] 

机构地区：[1]北京中医药大学,北京100029 [2]陕西中医药大学,咸阳712046

出　　处：《中华中医药杂志》2016年第5期1822-1827,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81373587);北京中医药大学研究生自主课题(No.2014-JYBZZ-XS-146);教育部中医养生学重点实验室;北京市中医养生学重点实验~~

摘　　要：目的:观察糖痹康对糖尿病大鼠坐骨神经Keap1/Nrf2信号通路的影响,探讨糖痹康防治糖尿病周围神经病变作用机制。方法:雄性SD大鼠,高脂饲料联合小剂量链脲佐菌素诱发糖尿病大鼠模型,造模成功后随机分为模型组、α-硫辛酸(ALA,0.0268g/kg)组,糖痹康高(2.5g/kg)、中(1.25g/kg)、低(0.625g/kg)剂量组,每组10只,另设10只雄性SD大鼠为正常组。实验中每4周检测大鼠体质量和随机血糖,干预12周后测大鼠右侧坐骨神经传导速度,行坐骨神经HE、Weil,s染色,Western blot检测大鼠坐骨神经中Keap1、Nrf2蛋白表达,实时荧光定量PCR检测大鼠坐骨神经Keap1、Nrf2、ARE m RNA的表达。结果:与模型组比较,ALA组、糖痹康高、中剂量组干预8周和12周时大鼠随机血糖显著降低(P<0.05,P<0.01);ALA组,糖痹康高、中剂量组干预12周后大鼠坐骨神经传导速度显著升高(P<0.01,P<0.05);光镜下显示各药物干预组均有效改善坐骨神经纤维结构。干预后,ALA组、糖痹康高、中剂量组Keap1蛋白及m RNA表达量都明显低于模型组(P<0.01,P<0.05),Nrf2的蛋白及m RNA表达量都明显高于模型组(P<0.01,P<0.05),ARE的m RNA表达量亦都明显高于模型组(P<0.01,P<0.05)。结论:糖痹康可能通过调节Keap1/Nrf2信号通路改善糖尿病大鼠坐骨神经损伤。To investigate the effects of Tangbikang（TBK） on Keap1/Nrf2 signal pathway of sciatic nerve of diabetic rats and explore the mechanism underlying TBK preventing and treating diabetic peripheral neuropathy. Methods： The diabetic rat model was established by high-fat diet combined with low dose of streptozotocin（STZ）. After modeling, diabetic rats were randomly divided into the model group, alpha lipoic acid（ALA, 0.0268 g · kg-1 · d-1） group, TBK high dose（2.5g/kg）, medium dose（1.25g/kg） and low dose（0.625g/kg） groups, 10 rats of each group, with excessive 10 rats as the control group. The rats＇ body weight and blood glucose were measured every 4 weeks during experiment. Twelve weeks later, the right sciatic nerve conduction velocity was measured, and morphological changes were observed by HE and Weil＇s staining. The proteins expression of Keap1 and Nrf2 were detected by Western blot. The m RNA expression of Keap1 Nrf2 and ARE were detected by real-time PCR. Results： At 8 and 12 weeks of treatment, compared with the model group, the blood glucose in ALA group and high and medium TBK groups were decreased. After 12 weeks of treatment, compared with the model group, the sciatic nerve conduction velocity in the ALA group and high and medium TBK groups were increased. The results of microscope showed that the structure of sciatic nerve fiber improved effectively in all treatment groups. After treatment, compared with model group, the protein and m RNA expression of keap1 were decreased in ALA and TBK of high and medium groups, while Nrf2 increased as well as the m RNA expression of ARE（P〈0.01, P〈0.05）. Conclusion： TBK may improve sciatic nerve damage of diabetic rats through the regulation of Keap1/Nrf2 pathway.

关 键 词：糖痹康 糖尿病周围神经病变 坐骨神经 Keap1/Nrf2信号通路 

分 类 号：R285.5[医药卫生—中药学]