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目的探讨酪氨酸激酶(Src)在蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)中的作用和机制,以及应用Src抑制剂PP2对脑血管痉挛的治疗作用。方法枕大池二次注血法制作大鼠SAH模型,造模后第1天至第5天腹腔注射10mmoL／L Sre抑制剂PP2 0．1ml,对照组注射等体积 DMSO。第5天处死动物,H-E染色观察大鼠基底动脉血管直径。Westemblot检测基底动脉Src、 Ras、MAPK蛋白表达,Real-time PCR检测基底动脉IL-1β、IL-6 mRNA表达。结果枕大池二次注血法成功制作SAH模型,基底动脉发生了明显血管痉挛。SAH组基底动脉Src、Ras、MAPK表达显著增高,IL-1β、IL-6细胞因子mRNA表达增加。应用PP2后血管痉挛减轻,基底动脉Src、Ras、 MAPK表达下降,IL-1β、IL-6 mRNA表达减少。结论 Src与SAH后脑血管痉挛发生有关。Src抑制剂PP2能够缓解脑血管痉挛,其机制一部分通过MAPK信号通路起作用,另外可能通过减少IL- 1β、IL-6等细胞因子表达,抑制炎症反应起作用,针对该信号通路可能对脑血管痉挛的治疗有效。
Objective To investigate the role and mechanism of tyrosine kinase (Src) in cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) and the therapeutic effect of Src inhibitor PP2 on cerebral vasospasm. Methods The rat model of SAH was established by the secondary injection of occipital cistern. The rats were injected intraperitoneally with 10 mmoL / L Sre inhibitor PP2 on day 1 to day 5, and the control group was injected with equal volume of DMSO. The animals were sacrificed on the 5th day and the diameter of the basilar artery in rats was observed by H-E staining. The expression of Src, Ras and MAPK in basilar artery was detected by Westemblot and the expression of IL-1β, IL-6 mRNA in basilar artery was detected by Real-time PCR. Results The model of SAH was successfully made by the secondary injection of occipital cistern and obvious vasospasm occurred in the basilar artery. SAH group basilar artery Src, Ras, MAPK expression was significantly increased, IL-1β, IL-6 cytokine mRNA expression increased. Vasospasm was relieved after application of PP2, the expression of Src, Ras and MAPK in basilar artery decreased and the expression of IL-1β and IL-6 mRNA decreased. Conclusion Src is related to the occurrence of cerebral vasospasm after SAH. Src inhibitor PP2 can relieve cerebral vasospasm, the mechanism of which partly through the MAPK signaling pathway, in addition may reduce the expression of IL-1β, IL-6 and other cytokines, inhibit the inflammatory response, the signal pathway may affect the cerebrovascular Treatment of spasticity effective.