氢吗啡酮对炎性痛大鼠脊髓ERK1/2信号通路的影响

Effect of Hydromorphine on ERK1/2 Signal Pathway in Spinal Cord of Rats with Inflammatory Pain

目的探讨氢吗啡酮对炎性痛大鼠脊髓ERK1/2信号通路的影响。方法选择SPF级雄性大鼠30只,随机分为3组,正常组、模型组和氢吗啡酮组;检测各组大鼠热痛阈和机械痛阈;ELISA检测血清中TNF-α、IL-6和IL-10的含量;Western blot检测各组大鼠脊髓中ERK1/2和p-ERK1/2蛋白表达水平;qRT-PCR法检测各组大鼠脊髓中ERK1/2 mRNA表达水平。结果与正常组相比,模型组大鼠血清炎症细胞因子TNF-α和IL-6含量明显增高,IL-10含量明显降低,且术侧后肢热痛阈显著缩短及机械痛域明显降低,差异均有统计学意义(P<0.05);脊髓中ERK1/2 mRNA表达水平、ERK1/2及p-ERK1/2蛋白表达水平均显著升高,差异有统计学意义(P<0.05)。注射氢吗啡酮后,与模型组相比,大鼠血清TNF-α和IL-6含量显著降低而IL-10含量显著升高,热痛阈显著延长及机械痛域明显升高,差异均具有统计学意义(P<0.05);氢吗啡酮组ERK1/2 mRNA表达水平、ERK1/2和p-ERK1/2蛋白表达水平均明显降低(P<0.05)。结论氢吗啡酮可有效改善弗氏完全佐剂诱导的大鼠炎性疼痛,其抗炎镇痛机制与降低大鼠机体炎性因子的产生,并抑制ERK1/2信号通路的活化有关。

Objective To investigate the effect of hydromorphine on ERK1/2 signal pathway in spinal cord of rats with inflammatory pain.Method Thirty SPF male rats were randomly divided into three groups:the normal group,the model group and the hydromorphine group.Detection of thermal pain threshold and mechanical pain threshold were detected in rats of each group.TNF-α,IL-6 and IL-10 in serum were tested by ELISA.Western blot detected the ERK1/2 and p-ERK1/2 protein expression in spinal cord of rats in each group.The expression of ERK1/2 mRNA in spinal cord of rats in each group was detected by qRT-PCR method.Result Compared with the normal group,the content of serum inflammatory cytokines TNF-αand IL-6 in the model group was significantly higher than that in the normal group,while the content of IL-10 in the model group was significantly lower than that in the normal group,and the thermal pain threshold was significantly shortened and the mechanical pain domain was significantly decreased in the model group(P<0.05).The expression levels of ERK1/2 mRNA,ERK1/2 and pERK1/2 protein in spinal cord of the model group were significantly higher than those of the normal group(P<0.05).After injection of hydromorphine,compared with the model group,the contents of serum TNF-αand IL-6 were significantly decreased,while the content of IL-10 was significantly increased,the thermal pain threshold was significantly prolonged and the mechanical pain domain was significantly increased(P<0.05).The expression of ERK1/2 mRNA,ERK1/2 and p-ERK1/2 protein decreased significantly in hydromorphine group(P<0.05).Conclusion Hydromorphine can effectively improve complete freund’s adjuvant-induced inflammatory pain in rats.Its anti-inflammatory and analgesic mechanism is related to its reduction of the production of inflammatory factors and inhibition of the activation of ERK1/2 signal pathway in rats.