【摘要】 目的探讨p38 MAPK信号通路在舒巴坦诱导大鼠脑缺血耐受中的作用。方法 25只无特定病原体的Wistar大鼠分为5组,每组5只。(1)假手术组:侧脑室注射生理盐水10μL,随后行全脑缺血的假手术,手术只暴露和分离双侧椎动脉及双侧颈总动脉,不阻断其血流;(2)全脑缺血组:首先侧脑室注射生理盐水10μL,随后即刻行8 min全脑缺血手术;(3)舒巴坦+全脑缺血组:首先给大鼠侧脑室注射舒巴坦溶液(360 nmol,10μL),随后即刻行8min全脑缺血手术;(4)SB203580+舒巴坦+全脑缺血组:首先给大鼠侧脑室注射SB203580溶液(5 nmol,10μL),30min后给予舒巴坦(360 nmol,10μL)侧脑室注射,随后即刻行8 min全脑缺血手术;(5)SB203580组:首先给大鼠侧脑室注射SB203580(5 nmol,10μL),30 min后按照假手术组的方法,注射生理盐水及行脑缺血假手术。末次手术后7 d处死动物,取脑组织进行硫堇染色,观察大鼠海马CA1区神经细胞的形态和神经细胞密度,并进行组织分级。结果全脑缺血组大鼠海马CA1区大片神经细胞破坏、死亡,细胞排列疏松、紊乱,散在大量细胞碎片,神经细胞密度降低明显,组织学分级明显升高;舒巴坦+全脑缺血组组织学分级明显减低,神经细胞密度明显升高;SB203580+舒巴坦+全脑缺血组神经细胞密度明显降低,组织学分级明显升高。结论 p38 MAPK参与了舒巴坦预处理诱导的大鼠脑缺血耐受。更多还原

【Abstract】 Objective To investigate the role of p38 MAPK signaling pathway in sulbactaminduced brain ischemic tolerance in rats. Methods The model of rat global cerebral ischemia was used.After a stainless steel cannula was implanted in the right lateral ventricle,25 healthy male Wistar rats were randomly divided into the following groups(n = 5 in each group).(1) Sham group(normal saline +sham) : the rats were administrated with normal saline of 10 μL via the cannula first,and then the sham operation for global cerebral ischemia was performed.(2) Global cerebral ischemia group(ischemia) :normal saline(10 μL) was administrated via the cannula first and then performed 8 minutes of global cerebral ischemia immediately.(3)Sulbactam+ischemic group: sulbactam solution(10 μL,360 nmol) was administrated via the cannula first and then performed 8 minutes of global cerebral ischemia immediately.(4)SB203580+sulbactam+ischemic group: SB203580(10 μL,5 nmol) was administrated via the cannula30 minutes before sulbactam(10 μL,360 nmol) and then performed 8 minutes of global cerebral ischemia immediately.(5)SB203580+sham group: SB203580 solution(10 μL,5 nmol) was administrated via the cannula first and then performed sham operation for global cerebral ischemia immediately. The neuropathological evaluation including histological grade(HG) and neuronal density(ND) was performed using the method of thionic staining to observe the survival situation of neurons in CA1 hippocampus.Results Global cerebral ischemia for 8 min induced obvious delayed neuronal death(DND) which resulted in large area of neuronal absence in the CA1 hippocampus with the significant increase in HG and decrease in ND. Pre-treatment with sulbactam effectively prevented the DND normally induced by the global brain ischemia. Compared with ischemic group,the HG was significantly reduced,and the ND increased significantly. Pretreatment with SB203580,an inhibitor of p38 MAPK signal pathway,blocked the neuroprotective effect mediated by sulbactam. Compared with sulbactam+ischemic group,the ND was significantly decreased,and the HG increased significantly. Conclusion p38 MAPK signaling pathway may participate in the sulbactam-induced brain ischemic tolerance in rats.更多还原