摘要目的 研究消退素D1对突出髓核所致根性神经痛的影响及内在机制.方法 选取56只雄性Sprague-Dawley(SD)大鼠,按照随机数字表法分为假手术组、模型组、消退素D1 10 ng组、消退素D1 100 ng组,每组14只,建立非压迫性椎间盘突出症模型.术后1d、2d、3d,假手术组和模型组分别注射磷酸盐缓冲液(PBS) 10 μl,消退素D1 10 ng组和消退素D1 100 ng组分别注射含有消退素D1 10 ng和100 ng的PBS10μl.于术前1d及术后连续7d分别检测各组大鼠术侧后肢50％缩足阈值(PWT).术后7d,取大鼠脊髓组织经酶联免疫吸附测定法(ELISA)检测肿瘤坏死因子(TNF-α)、白介素1β(IL-1β)和白介素10(IL-10)的蛋白表达量,采用蛋白质印记Western blot法检测脊髓组织中细胞外信号调节激酶(ERK)核转录因子NF-κB/p65(NF-κB/p65)的含量变化.结果 术后1d至7d,模型组大鼠50％ PWT较假手术组明显降低(P＜0.05);术后3d、4d、5d、6d、7d,消退素10 ng组与模型组比较,50％ PWT显著升高(P＜0.05);术后2d、3d、4d、5d、6d、7d,消退素100 ng组与模型组比较,50％ PWT显著升高(P＜0.05).与假手术组比较,模型组大鼠TNF-α和IL-1β的蛋白表达水平明显升高(P＜0.05),IL-10的表达水平明显降低(P＜0.05);与模型组比较,消退素10 ng组和消退素100 ng组的TNF-α和IL-1β的蛋白表达水平明显降低(P＜0.05),IL-10的表达水平明显升高(P＜0.05),且消退素100 ng组的蛋白含量下降更显著(P＜0.05).与假手术组比较,模型组p-ERK、NF-κB/p65蛋白水平明显升高(P＜0.05);与模型组比较,消退素10 ng组和消退素100 ng组p-ERK及NF-κB/p65蛋白水平明显降低(P＜0.05),且消退素100 ng组降低的更明显(P＜0.05).结论 消退素D1通过调节炎症介质表达及p-ERK和NF-κB/p65通路的活性,促进神经根炎症的消退,为治疗腰椎间盘突出症提供了新的思路.

abstractsObjective To investigate the analgesic effect of Resolvin D1 (RvD1) on radicular pain induced by herniated nucleus pulposusand its underlying mechanism.Methods Fifty-six male rats were randomly divided intoa sham group,a model group,a 10 ng group anda 100 ng group,each of 14.The rat model of non-compressive lumber disc herniation was established in all except the sham group.The former two groups were then injected with 10 μl of phosphate buffer solution (PBS) while the latter 2 groups were injected with 10 μl of PBS containing 10 and 100 ng of RvD1 respectively daily for three successive days.The rats' 50％ paw withdrawal threshold (PWT) was evaluated 1 day before and on 7 successive days after surgery.On day 7 the rats' spinal cords were removed to assess the expression of tumor necrosis factor-or (TNF-α),interlukin-1β (IL-1β) and interlukin-10 (IL-10) using ELISA methods.The levels of ERK and NF-κB/p65 were measured using Western blotting.Results Theaverage 50％PWT of the model group decreased significantly from day 1 to day 7 compared with the sham group,but was significantly lower thanthe RvD1 10 ng group from day 3 to day 7.Moreover the 50％PWT in the RvD1 100 ng group increased significantlyfrom day 2 to day 7 compared with the model group (P＜0.05).The average expression of both TNF-α and IL-1β of the model group was upregulated significantly and that of IL-10 decreased significantly compared with the sham group.Compared with the model group,the expression of TNF-α and IL-1β decreased significantly (P＜0.05)and the level of IL-10 was significantlyup-regulated (P＜0.05) both in the RvD1 10 ng group and 100 ng group.Moreover,the changes were larger in the RvD1 100 ng group (P＜0.05).Compared with the sham group,the levels of p-ERK and NF-κB/p65 in the model group were significantly up-regulated (P＜0.05).Compared with the model group,intrathecal injection of RvD1 (10 ng or 100 ng) significantly decreased the expressions of p-ERK and NF-κB/p65 (P＜0.05).Moreover,the decrease wasgreater in the RvD1 100 ng group (P＜0.05).Conclusions RvD1 might alleviate the radicular inflammation and pain byregulating the balance of inflammatory mediators and activation of p-ERK and NF-κB/p65 pathways.It may offer novel therapeutic approaches for the management of lumbar disc herniation.