蛇床子素对髓核致炎神经根痛大鼠脊髓背角p38 MAPK表达的影响  

Effect of osthole on p38 MAPK signaling related pathway of rat model with inflammatory radicular pain induce by nucleus pulposus in the spinal horn

作　　者：张嘉明 易增兴 林世清[4] 王益敏[4,2] 蔡哲 魏明 孙来保[1,2] 邹学农 

机构地区：[1]惠州市中大惠亚医院麻醉科,广东惠州516081 [2]广东省骨科学重点实验室,广东广州510080 [3]宜春学院化学与生物工程学院药学教研室,江西宜春336000 [4]中山大学附属第一医院麻醉科,广东广州510080 [5]中山大学附属第一医院脊柱外科,广东广州510080

出　　处：《中国药理学通报》2018年第2期237-243,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金重点项目(No 31430030);惠州市大亚湾科技计划项目(No 2014A01015)

摘　　要：目的研究蛇床子素(osthole,Ost)对髓核致炎神经根痛大鼠脊髓背角p38 MAPK信号相关通路表达的影响。方法♂成年SD大鼠156只随机分为5组:Blank组(n=36)、Sham组(n=36)、手术模型组(NP,n=36)、DMSO组(n=24)、蛇床子素组(Ost组,n=24),检测所有大鼠术前1 d,术后1、2、6、7、12、14、21、28 d的50%机械痛阈值(mechanical withdrawal threshold,MWT)。DMSO组和Ost组于术后d2经硬膜外腔分别注射100 m L·L^(-1)DMSO和20 g·L^(-1)蛇床子素,体积均为50μL。分别于术后7、14 d取出术侧腰段脊髓背角,Western blot检测p-p38、IL^(-1)8、IL^(-1)8R蛋白的表达,q PCR检测IL^(-1)8 mRNA表达。结果与Blank组相比,Sham组在术后1 d 50%MWT降低(P<0.05),而NP组、DMSO组及Ost组术后各时点的50%MWT降低(P<0.05);术后d 7 p-p38、IL^(-1)8蛋白及IL^(-1)8 mRNA表达上调(P<0.05),而IL^(-1)8R蛋白在术后d 14表达上调(P<0.05);硬膜外给予蛇床子素后,与DMSO组相比,Ost组各个时间点的50%MWT升高,持续至术后28 d(P<0.05),同时,术后d 7伴有p-p38、IL^(-1)8蛋白及IL^(-1)8 mRNA表达下降;术后d 14,IL^(-1)8R蛋白表达降低(P<0.05);p-p38蛋白相对浓度和IL^(-1)8 mRNA含量进行相关性分析,Spearman秩相关系数R=0.9(P<0.05)。结论髓核致炎大鼠脊髓背角p-p38蛋白及IL^(-1)8可能参与了早期炎性痛形成,而IL^(-1)8R在疼痛的维持中发挥作用,蛇床子素长期有效缓解髓核致炎大鼠神经根痛,可能与抑制p38 MAPK信号相关通路有关。Aim To observe the effect of epidurally application of osthole on the model of nucleus pulposusinduced inflammatory radicular pain and the expression of p38 MAPK signaling related pathway in the spinal dorsal horn of rats. Methods The model of radicular pain was generated by putting nucleus pulposus to the L5 dorsal root ganglion( DRG). 50% MWT was measured using Von Frey filaments to calculate mechanical pain threshold before and after operation. 50 μL of 20 g · L^(-1) osthole was administered epidurally in group Ost and 50 μL of 100 m L·L^(-1) DMSO in group DMSO at postoperative day( POD). The expression of phosphorylated p38( p-p38),IL^(-1)8 and IL^(-1)8 R in the lumbar spinal dorsal horn was detected by Western blot. IL^(-1)8 mRNA was assessed by real-time PCR.Results The mechanical pain threshold significantly decreased after operation( P < 0. 05),while the expression of protein p-p38 MAPK,IL^(-1)8,IL^(-1)8 R and IL^(-1)8 mRNA was significantly different. Compared with DMSO group,50% MWT was significantly increased and accompanied with the decrease of protein p-p38,IL^(-1)8,IL^(-1)8 R and IL^(-1)8 mRNA in Ost group after drug administration( P < 0. 05). The correlation analysis between protein concentration of p38 MAPK and IL^(-1)8 mRNA showed that the Spearman correlation coefficient was 0. 9( P < 0. 05). Conclusion p-p38 and IL^(-1)8 of spinal dorsal horn participate in the rat model with inflammatory radicular pain induced by nucleus pulposus,and IL^(-1)8 R plays a role in maintenance of the pain. Osthole administered epidurally in the early stage of pain could alleviate the pain for a long time,which may be related with inhibiting p38 MAPK signaling related pathways.

关 键 词：蛇床子素 脊髓背角 p38 MAPK信号通路 IL-18 IL-18R 神经根炎性痛 

分 类 号：R-332[医药卫生] R284.1