神经生长因子在紫杉醇诱发神经病理性痛模型大鼠脊髓背角和背根神经节中的表达

摘要

Objective:To investigate the dynamic expression of nerve growth factor (NGF) in the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) of rats with paclitaxel-evoked neuropathic pain (NP) and the pain behavioral changes.Methods:Twenty six weeks old male SD rats weighting 200 ～ 220 g were randomly divided into two groups:normal control group (group C,n =10) and paclitaxel group (group P,n =10).Rats were given ip injections of paclitaxel (2 mg/kg) every other day in group P,and an equal volume of saline in group C (4 times total).Body weight and pain behavioral changes were measured before treatment and on days 7,14 and 21 after injection.The expression of NGF in L4-6 SD and DRG was measured by Western blot in 6 rats on the 21st day,and the immunohistochemistry of NGF was tested in 4 rats at the same time.Results:In paclitaxel group,mechanical hyperalgesia appeared on the 7th day and mechanical allodynia appeared on the 14th day after paclitaxel administration,then until the 21st day.The expression of NGF in the SDH and DRG of rats in paclitaxel group was significantly higher than that in normal control group (P ＜ 0.05),and the protein level of NGF was positively correlated with pain behavioral changes.Conclusion:NGF plays an important role in spinal cord pain processing and central sensitization of rats with paclitaxel-evoked neuropathic pain (NP).%目的:观察大鼠腹腔注射紫杉醇诱发神经病理性痛(neuropathic pain,NP)后疼痛行为学变化以及神经生长因子(nerve growth factor,NGF)的表达.方法:健康雄性SD大鼠20只,6周龄；采用随机数字表法将其随机均分为2组(n=10):空白对照组(control group,C组)和紫杉醇制模组(paclitaxel group,P组).P组隔日腹腔注射紫杉醇2 mg/kg,共4次；C组隔日腹腔注射生理盐水1 ml/kg,共4次.在制模前及制模后第7、14天和第21天测定大鼠体重及疼痛行为学变化.给药结束后第21天时,处死大鼠；每组分别对6只大鼠进行蛋白质免疫印迹法(Western blot法)测定,对4只大鼠进行免疫组织化学染色法测定,以确定各组大鼠L4～6脊髓背角和背根神经节中神经生长因子(nerve growth factor,NGF)的表达水平.结果:紫杉醇制模组大鼠在制模后第7天即出现痛觉过敏,第14天出现触诱发痛,并持续至21天,疼痛程度显著大于空白对照组(P＜0.05)；且NGF在脊髓背角和背根神经节中的表达相比空白对照组显著增加(P＜0.05).大鼠NGF的表达与行为学的改变呈正相关(r=0.677,P＜0.01).结论:NGF在紫杉醇诱发的神经病理性痛大鼠中枢敏化中有重要作用.