酪氨酸激酶抑制剂对大鼠蛛网膜下腔出血后脑血管痉挛的作用研究  

The effects of Src inhibitor PP2 on cerebral vasospasm after experimental subarachnoid hemorrhage in rats

作　　者：高成[1] 刘相轸[1] 刘巍[2] 赵振环[1] 陈会荣[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院神经外科,150001 [2]哈尔滨医科大学第一临床医学院心内科,150001

出　　处：《中华神经外科杂志》2006年第3期177-180,共4页Chinese Journal of Neurosurgery

基　　金：黑龙江省自然科学基金资助(D200530)

摘　　要：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 effects of Src tyrosine kinase in the development of cerebral vasospasm after subarachnoid hemorrhage. To observe the therapeutic effect of PP2, an inhibitor of src, on cerebral spasms. Methods Auto-blood was injected into the cisern magna of the male Wistar rats on day 0 and day 2 to induce subarachnoid hemorrhage. From day 1 to day 5, 0.1 ml of 10 mmol/L PP2, the inhibitor of Src was injected intraperitoneally. The control group was given with equal volume of DMSO. On day 5, the diameter of basilar artery was measured using H- E staining. The protein of Src, Ras and MAPK in basilar artery was detected by Western blotting. The mRNA of IL-1β,IL-6 in basilar artery was determined using real-time RT-PCR. Results Src, Ras and MAPK protein in basilar artery was increased significantly after subarachnoid hemorrhage. PP2 can inhibit the Src, Ras and MAPK expression and attenuated the cerebral vasospasm. IL-1β, IL-6 mRNA was increased after subarachnoid hemorrhage significantly and down-regulated with injection of PP2. Conclusions Src tyrosine kinase plays an important role in the development of CVS after SAH. Inhibition of Src tyrosine kinase by PP2 can attenuate the cerebral vasospasm. The effects were partly mediated through MAPK signal transduction pathway and partly contributed to the inhibition of cytokine expression. Src tyrosine kinase may be a target for the treatment of cerebral vasospasm after SAH.

关 键 词：蛛网膜下腔出血 脑血管痉挛 酪氨酸激酶 细胞因子 

分 类 号：R743.35[医药卫生—神经病学与精神病学] R979.1[医药卫生—临床医学]