前列腺炎SB203580镇痛模型大鼠脊髓p38MAPK的表达变化及意义

Role of p38MAPK expression in spinal cord in analgesia for prostatitis with intrathecal SB203580 in a murine model

目的观察p38丝裂原活化蛋白激酶(p38MAPK)活性抑制剂SB203580鞘内注射对前列腺炎镇痛模型大鼠脊髓p38MAPK表达的影响。方法45只SPF级雄性SD大鼠随机分为3组:对照组(5只)、前列腺炎组(10只)和前列腺炎SB203580鞘内注射镇痛组(镇痛组,30只)。镇痛组再均分3个亚组,通过前列腺注射完全弗氏佐剂(CFA),并经脊髓鞘内分别注射SB2035800.5、2.5和12.5μg/10μl。前列腺炎组和各镇痛亚组分别于给药或建模后5、10d处死5只大鼠,采用Western blotting和ELISA法检测各组大鼠L5-S2脊髓背角组织磷酸化p38MAPK(p-p38MAPK)、神经胶质酸性蛋白(GFAP)蛋白含量及肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)水平和一氧化氮合酶(iNOS)的活性变化。结果前列腺炎组大鼠L5-S2脊髓背角中p-p38MAPK、GFAP、TNF-α、NO水平和iNOS活性在5d和10d均明显高于对照组,并随时间延长增高(P<0.01)。镇痛组大鼠L5-S2脊髓背角中p-p38MAPK、GFAP、TNF-α、NO水平和iNOS活性在5d和10d均低于前列腺炎组,且呈剂量依赖效应(P<0.01)。结论脊髓p38MAPK信号通路参与了大鼠前列腺炎发生后的脊髓痛觉传导及SB203580镇痛机制,阻断p38MAPK信号通路可有效降低脊髓炎性因子水平。

Objective To investigate the expression of p38 mitogen-activated protein kinase （p38MAPK） in posterior horn of L5 - S2 spinal cord in analgesia for chronic prostate pain with intrathecal injection of SB203580 （p38MAPK inhibitor activity） in a murine model. Methods Forty-five male SPF SD rats were randomly divided into control group （n=5）, prostatitis group （n=10） and SB203580 analgesia group （n=30, SB203580 was intrathecally injected）. In the SB203580 analgesia group, complete Freunds adjuvant was injected into the prostate and SB203580 of 0. 5μg/10μl, 2. 5μg/10μl and 12. 5μg/10μl was intrathecally injected respectively. Five days and ten days after drug administration or simple modeling, phosphorylated p38MAPK （p-p38MAPK）, glial fibrillary acidic protein （GFAP）, tumor necrosis factor-α （TNF-α）, nitric oxide （NO） level and induced nitric oxide synthase （iNOS） activity of L5 -S2 spinal dorsal horn of rats were determined by Western blotting and ELISA assay, respectively. Results In the prostatitis group, the p-p38MAPK, GFAP, TNF-α, NO level and iNOS activity of L5 -S2 spinal dorsal horn of rats at the 5th day and the 10th day were significantly higher than those of the control group and increased with time. The p-p38MAPK, GFAP, TNFα, NO levels and iNOS activity at the 5th day and 10th day in SB203580 analgesia group were lower than those in the prostatitis group. Conclusion P38MAPK signaling pathway was involved in the mechanism of pain conduction and analgesia by SB203580 after prostatitis. The level of inflammatory factors in spinal cord can be effectively reduced by blocking the p38MAPK signaling pathway.