JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用

Effect of JNK / MCP-1 signaling pathway on anti-diabetic neuropathic pain by curcumin in type 2 diabetic rats

目的：观察JNK/MCP-1通路在姜黄素抗大鼠糖尿病神经病理性疼痛（DNP）中的作用及机制。方法：雄性SD大鼠诱导为2型糖尿病神经病理性痛大鼠（DNP）模型,将其随机分为6组（n=27）：DNP组、姜黄素组（Cur组）、溶剂对照组（DSC组）、JNK抑制剂组（DJ组）、JNK抑制剂溶剂对照组（DJS组）、姜黄素＋单核细胞趋化蛋白1（MCP-1）激动剂组（DM组）。另取27只正常大鼠为正常对照组（C组）,给药后3 d、7 d、14 d时测定机械缩足痛阈和热缩足潜伏期,并在同一时点取脊髓腰膨大及L4-6背根神经节（DRG）,用免疫印迹法测定脊髓和DRG中p-JNK水平,用ELISA测定脊髓和DRG中的MCP-1含量。结果：与DNP组相比,在给药后的7 d、14 d Cur组、DJ组、DM组p-JNK的表达明显下降（P〈0.05）;与C组相比,链脲佐菌素给药后其它6组MCP-1含量出现明显下降;与DNP组相比,在给药后的7 d、14 d Cur组、DJ组MCP-1出现明显上升,而DM组出现进一步下降（P〈0.05）。结论：DNP大鼠脊髓和DRG中的p-JNK、MCP-1表达明显升高,姜黄素减轻2型糖尿病大鼠神经病理性疼痛的机制可能与JNK/MCP-1信号通路有关。

AIM： To investigate the effect of JNK/MCP-1 signaling pathway on anti-diabetic neuropathic pain by curcumin in type 2 diabetic rats. METHODS： The male Sprague-Dawley rats were induced as the model of the type 2diabetic neuropathic pain rats,they were randomly divided into 6 groups（ n = 27） ： type 2 diabetic neuropathic pain（ DNP） group,type 2 diabetic neuropathic pain and intraperitoneal injection of curcumin（ Cur） group,type 2 diabetic neuropathic pain and solvent control（ DSC） group,type 2 diabetic neuropathic pain and JNK inhibitor（ DJ） group,type 2diabetic neuropathic pain and JNK inhibitor solvent control（ DJS） group,type 2 diabetic neuropathic pain and monocyte chemoattractant protein 1（ MCP-1） agonist（ DM） group. Another 27 normal SD rats were selected as control group. Mechanical withdrawal threshod and thermal withdrawal latency were measured at 3rd d,7th d and 14 th d after dosing,then the lumbar segment 4 - 6 of the spinal cord and L4 - 6 DRG were removed at the same time. ELISA was used to measure MCP-1 level. The expression of p-JNK was determined by Western blotting. RESULTS： Compared with DNP group,pJNK was significantly decreased at 7th d and 14 th d in Cur group,DJ group and DM group after treatment（ P〈0. 05）.Compared with C group,the MCP-1 was significantly declined in other 6 group after streptozotocin injection（ P〈0. 05）.Compared with DNP group,MCP-1 were significantly increased at 7th d and 14 th d in Cur group and DJ group after treatment（ P〈0. 05）,and that in DM group was greatly decreased（ P〈0. 05）. CONCLUSION： The expression of p-JNK and MCP-1 was increased in DNP rats with spinal cord and dorsal root ganglion. The mechanism of curcumin reducing the neuropathic pain in type 2 diabetic rats might be through regulating the JNK / MCP-1 pathway.