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。
Objective:To investigate the effects of curcumin on pain threshold and the expressions of nuclear factorκB(NF-κB)and CX3C chemokine receptor 1(CX3CR1)in spinal cord and dorsal root ganglion(DRG)of the rats with sciatic nerve chronic constrictive injury.Methods:One hundred and twenty male Sprague Dawley rats,weighing 220-250 g,were randomly divided into 4 groups.Sham surgery(sham)group:the sciatic nerves of rats were only made apart but not ligated;chronic constrictive injury(CCI)group:the sciatic nerves of rats were only ligated without any drug treatment;curcumin treated injury(Cur)model group:the rats were administrated with curcumin 100 mg/(kg·d)by intraperitoneal injection for 14 days after CCI;solvent control(SC)group:the rats were administrated with the solvent at the same dose for 14 days after CCI.Thermal withdrawal latency(TWL)and mechanical withdrawal threshold(MWT)of rats were respectively measured on pre-operative day 2 and postoperative day 1,3,5,7,10 and 14.The lumbar segment L4-5 of the spinal cord and the L4,L5 DRG was removed at post-operative day 3,7 and 14.The change of nuclear factorκB(NF-κB)p65 expression was detected by Western blotting while the expression of CX3CR1 was determined by immunohistochemical staining.Results:Compared with the sham group,the TWL and MWT of rats in the CCI group were significantly decreased on each post-operative day(P〈0.01),which reached a nadir on the 3rd day after CCI,and the expressions of NF-κB p65and CX3CR1 were markedly increased in spinal cord dorsal horn and DRG.In the Cur group,the TWL of rats were significantly increased than those in the CCI group on post-operative day 7,10 and 14(P〈0.05)and MWT increased than those in the CCI group on post-operative day 10 and 14(P〈0.05).In addition,the administration of curcumin significantly decreased the positive expressions of NF-κB p65 and CX3CR1 in spinal cord and DRG(P〈0.05).Conclusion:Our study suggests that curcumin cou