MCC950下调即早基因的表达缓解甲醛所致小鼠炎性痛

MCC950 alleviating inflammatory pain induced by formaldehyde through down-regulation of immediate early genes in mouse spinal cord

目的探讨MCC950对甲醛模型小鼠疼痛的影响及可能机制。方法 72只ICR雄性小鼠随机分为生理盐水对照组(NS组),甲醛模型组(F组)、不同浓度梯度MCC950干预组(6.25 mg/kg MCC950+F、12.5 mg/kg MCC950+F、25 mg/kg MCC950+F、50 mg/kg MCC950+F)。以小鼠累计舔咬足时间评价自发痛行为;采用Real-time PCR方法检测小鼠脊髓即早基因,包括c-Fos、Arc、早期生长反应因子-1(Egr-1) mRNA的表达变化;采用免疫组织化学法检测脊髓背角内c-Fos的表达。结果自发痛评分显示,与NS组相比,F组小鼠出现典型双相痛;与F组相比,12.5 mg/kg、25 mg/kg及50 mg/kg MCC950预处理均可显著缓解甲醛所致小鼠疼痛。Real-time PCR结果显示,与NS组相比,F组小鼠脊髓早期基因(c-Fos、Arc、Egr-1)的mRNA表达均上调,50 mg/kg MCC950预处理后,上述指标的mRNA表达均显著下调。免疫组织化学结果显示,与NS组相比,F组小鼠脊髓背角c-Fos表达明显增加,而用50 mg/kg MCC950预处理后,小鼠脊髓背角c-Fos表达下降。结论 MCC950可有效缓解甲醛所致小鼠炎性痛,其机制可能与下调脊髓即早基因(c-Fos、Arc、Egr-1)的表达有关。

Objective To investigate the effect of MCC950 on inflammatory pain induced by formaldehyde in mice. Methods Seventy-two male ICR mice were randomly divided into six groups,including saline control group( NS),formaldehyde model group( F),different doses of MCC950 intervention group( 6. 25 mg/kg MCC950 + F,12. 5 mg/kg MCC950+F,25 mg/kg MCC950+F,50 mg/kg MCC950+F). The spontaneous pain was determined by the cumulative time of licking paw in mice. The expressions of immediate early genes( IEGs),such as c-Fos,Arc,early growth response protein 1( Egr-1),in the spinal cord were determined by Real-time PCR. The expression of c-Fos in the spinal cord was determined by immunohistochemistry. Results Spontaneous pain score showed that compared with the NS group,F group showed typical biphasic pain,however 12. 5 mg/kg,25 mg/kg and 50 mg/kg MCC950 intervention decrease significantly the second phase pain compared with the F group. The result of Real-time PCR showed that the mRNA level of c-Fos,Arc and Egr-1 in the spinal cord of F group enhanced remarkably compared with the NS group,while it could be reversed by50 mg/kg MCC950 treatment. The result of immunohistochemistry showed that the number of c-Fos positive cells in the posterior horn of spinal cord of the F group increased significantly compared with the NS group,while it could be reversed by the treatment with 50 mg/kg MCC950. Conclusion MCC950 can alleviate the inflammatory pain induced by formaldehyde in mice,which may be related to the down-regulation of IEGs in the spinal cord.