加味黄芪桂枝五物汤对糖尿病周围神经病变大鼠神经行为学及miR-146a炎症通路的影响  

Effects of Modified Huangqi Guizhi Wuwu Decoction on neuroethology and miR-146a inflammatory pathway in diabetic peripheral neuropathy rats

作　　者：郭咏梅[1] 钟兆怡 王明哲[1] 龚帆[1] 王骏[1] 张红智[1] 秦保锋[1] GUO Yongmei;ZHONG Zhaoyi;WANG Mingzhe;GONG Fan;WANG Jun;ZHANG Hongzhi;QIN Baofeng(Departmentof Neurology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院神经内科,上海201203

出　　处：《上海中医药杂志》2020年第S01期186-189,共4页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局第六批全国老中医药专家学术经验继承项目[国中医药人教发(2017)29];上海市进一步加快中医药事业发展三年行动计划中西医结合人才计划项目(ZY3-RCPY-4-2019);上海中医药大学课程建设项目;第五批曙光高级中医师项目.

摘　　要：目的观察加味黄芪桂枝五物汤对糖尿病周围神经病变大鼠神经行为学、痛阈值和血清中miR-146a、白介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)的影响。方法采用一次性腹腔内注射链脲佐菌素(STZ)60 mg/kg的方法制造糖尿病大鼠模型。随机分为6组,进行50%机械缩足阈值(PWT)测定,完成糖尿病神经病变(DPN)模型。成模后,加味黄芪桂枝五物汤低、中、高剂量组和英夫利昔单抗组分别给予相应药物干预,正常组和模型组予以0.9%NaCl溶液。检测治疗后各组时间点的血糖、坐骨神经传导速度(NCV)、机械痛阈的变化,并检测大鼠血清中miR-146a、IL-1β、TNF-α的表达情况。结果①各治疗组血糖与模型组相比无差异(P>0.05)。②糖尿病大鼠坐骨神经传导速度较正常组明显减慢,中药组及英夫利昔单抗组均能改善糖尿病大鼠坐骨神经传导速度,差异具有统计学意义(P<0.01),且中药高剂量组在16周时的疗效优于英夫利昔单抗组(P<0.05)。③药物干预后不同时间点,与模型组相比,各中药组大鼠PWT差异显著(P<0.05)。④加味黄芪桂枝五物汤组及英夫利昔单抗组均能升高miR-146a,降低IL-1β、TNF-α,与模型组相比差异显著(P<0.05);高剂量组有更加明显的改善效果(P<0.05)。结论加味黄芪桂枝五物汤可提高糖尿病周围神经病变大鼠运动神经传导速度、提高机械痛阈值,通过上调miR-146a,进而抑制IL-1β,TNF-α激活,从而减少炎症因子的表达,减轻炎症反应。Objective To observe the effects of Modified Huangqi Guizhi Wuwu Decoction on neuroethology,pain threshold and serum levels of miR-146 a,IL-1β,TNF-αin diabetic peripheral neuropathy rats.Methods A diabetic rat model was established by one time intraperitoneal injection of streptozotocin(STZ)at 60 mg/kg.The rats were randomly divided into 6 groups,the 50%paw withdrawal threshold(PWT)was measured,and the diabetic neuropathy(DPN)model was completed.After modeling,the Modified Huangqi Guizhi Wuwu Decoction groups with low-,medium-and high-dose and the Infliximab group were treated with the corresponding drugs,respectively,and the normal group and model group were treated with 0.9%NaCl solution.The changes of blood glucose,sciatic nerve conduction velocity(NCV)and mechanical pain threshold were measured at each time point after treatment,and the expressions of miR-146 a,IL-1βand TNF-αin serum of rats were detected.Results①There was no difference in blood glucose between the treatment groups and the model group(P>0.05).②The sciatic nerve conduction velocity of diabetic rats was significantly slower than that of the normal mice.The sciatic nerve conduction velocity of diabetic rats was improved in the Chinese medicine-treatment groups and the Infliximab group,with statistically significant difference(P<0.01),and the effect of the Chinese medicine-treatment group with high-dose was better than that of the Infliximab group at week 16(P<0.05).(3)At each time point after treatment,there was statistically significant difference in PWT between the model group and the Chinese medicine-treatment groups(P<0.05).(4)Compared with the model group,the level of miR-146 a was increased and the levels of IL-1βand TNF-αwere decreased in the Modified Huangqi Guizhi Wuwu Decoction groups and Infliximab group,with statistically significant differences(P<0.05),and the effect of the high-dose group was more significant(P<0.05).Conclusion Modified Huangqi Guizhi Wuwu Decoction can increase the motor nerve conduction velocity and mec

关 键 词：糖尿病周围神经病变 炎症反应 加味黄芪桂枝五物汤 MIR-146A 

分 类 号：R285.5[医药卫生—中药学]