补阳还五汤减轻脑梗死小鼠神经损伤的作用机制

Mechanism of Buyang Huanwu Decoction on Alleviates Neuronal Injury of Cerebral Infarction Model of Mice

目的研究白细胞介素1受体相关激酶M(IRAKM)在脑缺血-再灌注小鼠模型中介导补阳还五汤的脑保护作用。方法制备45 min小鼠大脑中动脉梗死(MCAO)模型,观察补阳还五汤在假手术和模型小鼠脑内诱导IRAKM的表达情况,多普勒监测大脑中动脉区域血流,荧光定量聚合酶链反应(PCR)检测IRAKM基因敲除小鼠脑内炎症因子的表达,TTC染色以显示脑梗死体积,并分别在给药组和对照组间、基因敲除和同笼繁殖野生小鼠间进行对比。结果补阳还五汤在假手术和脑梗死小鼠中均能显著诱导IRAKM基因表达。IRAKM基因缺失导致炎症因子转录激活进一步增强,包括肿瘤坏死因子(TNF-α)、诱导型一氧化氮合酶(iNOS)和环氧化酶(COX-2)。IRAKM基因敲除可明显加剧脑梗死的组织损伤并削弱补阳还五汤的脑保护作用。结论补阳还五汤可通过诱导IRAKM在脑内的表达发挥脑保护作用。

Objective To investigate the role and the mechanism of interleukin 1 receptor associated kinase M(IRAKM)in the protection of Buyang Huanwu Decoction(BHD)against neuronal injury in the model cerebral ischemia-reperfusion in mice.Methods Mice cerebral middle artery occlusion model(MCAO)was employed.IRAKM expression was observed in both Sham operative and model mice after administration of BHD.Transcranial doppler was used to monitor the blood flow of MCA territory.Fluorescent quantitative PCR was used to determine the expression of inflammatory factors in the brains from IRAKM knockout and wild-type mice.TTC staining was employed to observe the infarct volume in mice brain between vehicle and BHD treatment,or between IRAKM KO and WT littermates.Results BHD could significantly induce the expression of IRAKM gene in the brains from both Sham operative and MCAO mice.IRAKM gene deficiency induced further transcriptional activation of inflammatory factors,including tumor necrosis factorα(TNF-α),induction nitric oxide synthase(iNOS)and cyclooxygenase 2(COX-2).Knockout of IRAKM gene could obviously exacerbate neuronal injury and weaken the cerebra-protective effect of BHD in ischemia-reperfused mice.Conclusion BHD protects brain against ischemia-reperfusion through induction of IRAKM.