从CX3CR1通路探讨天麻素对化疗痛的作用机制  

Effect of gastrodin on chemotherapy-induced neuropathic pain and its mechanism： an analysis via CX3CR1 pathway

作　　者：罗妮[1] 宫登辉[1] 郑卫红[1] 郑军[2] 张金芝[1] 万君[1] 李余星 

机构地区：[1]三峡大学医学院国家中药药理三级实验室,宜昌443002 [2]三峡大学医学院外科教研室,宜昌443002

出　　处：《中华神经医学杂志》2015年第7期695-699,共5页Chinese Journal of Neuromedicine

基　　金：湖北省自然科学基金（2013CFC066）;宜昌市科学研究与开发项H（A13301-57）：三峡大学硕士学位论文培优基金（2014PY048）

摘　　要：目的探讨天麻素对化疗药物诱导的神经病理性疼痛的抑制作用及其机制。方法根据痛阈值大小筛选出合格的SD大鼠50只，采用随机数字表法分为5组：对照组、模型组、天麻素30mg／kg组、天麻素60mg／kg组、天麻素120mg／kg组，每组10只。用隔日腹腔注射长春新碱（125μg／kg）的方法建立化疗药物诱导的神经病理性疼痛动物模型（对照组大鼠除外），建模后第9天开始，继续腹腔注射长春新碱（125μg／kg），并开始采用不同剂量的天麻素治疗后3组大鼠。对照组和模型组用生理盐水（腹腔注射，5mL/kg）同步对照。治疗1周后（建模后第16天）分别用Electronic vonfrey测痛仪和热刺痛仪再次测定大鼠机械刺激痛阈值和热刺激痛阈值。Western blotting法检测脊髓CX3CR1蛋白和磷酸化p38MAPK蛋白表达，ELISA法检测脊髓TNF-α蛋白表达。结果与对照组比较，模型组大鼠机械痛阈值和热痛阈值明显降低，差异有统计学意义（P〈0．05），脊髓CX3CR1蛋白、p-p38MAPK蛋白和TNF-α蛋白表达显著升高，差异有统计学意义（P〈0．05）；与模型组比较，天麻素60mg／kg组、120mg／kg组大鼠机械痛阈值与热痛阈值有不同程度的升高，差异有统计学意义（尸l〈0．05），脊髓CX3CR1蛋白、p-p38MAPK蛋白和TNF-α蛋白表达有不同程度的降低，差异有统计学意义（P〈0．05）。结论天麻素能够抑制化疗痛大鼠机械痛阈值和热痛阈值，其发挥作用的机制可能与其抑制大鼠脊髓小胶质细胞活化通路中的CX3CR1、p-p38MAPK蛋白．进而减少炎性细胞因子TNF-α的表达相关。Objective To observe the inhibited effect of gastrodin on chemotherapy-induced neuropathic pain and its mechanism. Methods Filly SD rats, chosen according to the threshold of pain, were randomly divided into 5 groups（n=10）： control group, model group, and gastrodin treatment groups （30 mg/kg, 60 mg/kg and 120 mg/kg）. Vincristine （125 μg/kg, i.p.） was administered on alternate days to establish chemotherapy-induced neuropathic pain models in the model group and gastrodin treatment groups, and then, on the 9^th d of modeling rats in the gastrodin treatment groups were treated with different doses of gastrodin, while those in the control group and model group were given normal saline on the 16^th d of modeling. Paw withdrawal mechanical threshold and thermal pain threshold were measured; protein expressions of CX3CR1 and p-p38MAPK were detected by Western blotting, and tumor necrosis factor α （TNF-α） protein expression was detected by ELISA. Results As compared with control group, model group had significantly decreased pain threshold and increased protein expressions of CX3CR1, p-p38MAPK and TNF-α （P〈0.05）; as compared with those in the model group, the pain threshold increased and the expressions of CX3CR1, p-p38MAPK and TNF-α decreased in 60 mg/kg and 120 mg/kg gastrodin treatment groups, with significant differences （P〈0.05）. Conclusion Gastrodin can relieve the chemotherapy-induced neuropathic pain, probably by inhibiting the expressions of CX3CR1 and p-p38MAPK in the activation passageway of microglial cells in the spinal cord, and then, reducing the expression of TNF-α.

关 键 词：长春新碱 化疗痛 小胶质细胞 

分 类 号：R730.53[医药卫生—肿瘤]