吕翠岩　张胜容　徐暾海　孙文　赵文景　张竹华　郑桂敏　孟元　王晖　刘铜华

摘要：目的 观察中药复方糖痹康对糖尿病大鼠坐骨神经p38丝裂素活化蛋白激酶（p38 MAPK）及血浆肿瘤坏死因子-α（TNF-α）表达的影响，探讨其神经保护及镇痛机制。方法 SD雄性大鼠60只，随机选取10只为正常组，其余大鼠采用高脂饲料和小剂量链脲佐菌素诱发2型糖尿病大鼠模型。成模后随机分为模型组、甲钴胺组和糖痹康低、中、高剂量组，每组10只。各给药组给予相应药物干预。16周后取大鼠一侧坐骨神经，放免法检测大鼠血浆TNF-α含量；Western blot检测大鼠坐骨神经p38、p-p38 MAPK蛋白表达。结果 与正常组比较，模型组大鼠坐骨神经p38、p-p38蛋白表达及血浆TNF-α含量升高（P<0.05，P<0.01）；与模型组比较，各给药组大鼠血浆TNF-α含量和坐骨神经p-p38蛋白表达显著降低（P<0.05，P<0.01），各给药组p38蛋白表达降低，但只有糖痹康高剂量组差异有统计学意义（P<0.05）。结论 糖痹康下调大鼠坐骨神经p38、p-p38 MAPK蛋白表达和血浆TNF-α含量，可能是其糖尿病周围神经病变神经保护及镇痛作用靶点之一。

关键词：糖痹康；糖尿病周围神经病变；p38丝裂原活化蛋白激酶；肿瘤坏死因子-α；大鼠

DOI：10.3969/j.issn.1005-5304.2016.03.018

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）03-0067-03

Abstract： Objective To explore the effects of Chinese herbal compound Tangbikang on the expressions of p38 MAPK of sciatic nerve and plasma TNF-α in diabetic rats. Methods Ten of the sixty male SD rats were selected randomly as normal group， and the rest were fed with high-fat diet and low-dosage STZ was used to induce type Ⅱ diabetic rat models. Model rats were randomly divided into model group， mecobalamine group and Tangbikang low-， medium-， and high-dosage groups， 10 rats in each group. Each medication group was intervened with relevant medicine. Rat unilaterals sciatic nerves were taken after 16 weeks. The content of TNF-α in plasma was determined by radioimmunoassay. Western blot method was used to detect the expressions of p38 and p-p38 MAPK protein of sciatic nerve. Results Compared with normal group， the expressions of p38 and p-p38 protein and content of TNF-α in model group significantly increase （P<0.05， P<0.01）. Compared with the model group， the expressions of p-p38 protein and the content of TNF-α significantly decreased after medicine intervention in different doses Tangbikang groups and mecobalamin group （P<0.05， P<0.01）. The expression of p38 protein in Tangbikang high-dose group significantly decreased （P<0.05）， with statistical significance （P<0.05）. Conclusion Tangbikang can reduce the expression of p38 and p-p38 MAPK protein of the rat sciatic nerve， and reduce the content of TNF-α protein in rat plasma， which may be one of the effective targets of neuroprotection and abirritation of diabetic peripheral neuropathy.

Key words： Tangbikang； diabetic peripheral neuropathy； p38 MAPK； TNF-α； rats

糖尿病周围神经病变（diabetic peripheral neuropathy，DPN）是由糖尿病导致的周围神经系统病变，特点是由于对称的远端周围神经组织退化，导致其感觉的痛苦和缺失。本实验在前期研究基础上，采用高脂饲料和小剂量链脲佐菌素（STZ）诱发2型糖尿病大鼠模型，观察中药复方糖痹康对模型大鼠坐骨神经p38丝裂素活化蛋白激酶（mitogen activated protein kinase，p38 MAPK）及血浆肿瘤坏死因子-α（TNF-α）表达的影响，探讨其神经保护及镇痛机制。

1 实验材料

1.1 动物

6周龄SPF级SD雄性大鼠60只，体质量（160±10）g。许可证号SCXK（京）2004-0009，北京维通利华动物实验中心。北京中医药大学实验动物中心饲养，温度（23±2）℃，湿度（55±10）%，光照12 h，噪音<60 dB，自由摄食饮水，分笼喂养。

1.2 药物与饲料

糖痹康由黄芪、女贞子、桂枝、黄芩、黄连等组成，饮片由北京中医药大学中药学院提供；……