黄芪甲苷和羟基红花黄色素A配伍抗脑缺血再灌注损伤的协同作用及机制研究

摘要

目的 探讨黄芪甲苷(AST-Ⅳ)和羟基红花黄色素A(HSYA)配伍治疗大鼠脑缺血再灌注损伤作用及其机制.方法 100只大鼠随机分为假手术组、模型组、AST-Ⅳ组、HSYA组、AST-Ⅳ和HSYA配伍组等5组,采用线栓法建立大脑中动脉闭塞(MCAO)模型,再灌注72 h评分后处死;脑组织制片后采用苏木素-伊红(HE)染色,免疫组化检测血小板-内皮细胞粘附分子(CD31)表达;氧化炎症检测超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)指标.结果 与模型组比较,各给药组均有疗效,AST-Ⅳ组、HSYA组、AST-Ⅳ和HSYA配伍组均能改善大鼠神经损伤并减轻脑缺血再灌注损伤,促进CD31表达,改善SOD和谷胱甘肽过氧化物酶(GSH-Px)活性,降低TNF-α和IL-β水平,其中配伍组的治疗效果最为显著.结论 AST-Ⅳ和HSYA配伍可以显著发挥协同抗脑损伤作用,其抗炎、抗氧化和促血管新生作用是潜在作用机制.%Objective The effects and mechanism of astragaloside Ⅳ (AST-Ⅳ) and hydroxysafflor yellow A (HSYA) in combination against cerebral ischemia reperfusion in rats were studied.Methods One hundred Sprague Dawley rats were randomly divided into sham group,model group,AST-Ⅳ group,HSYA group and AST-Ⅳ + HSYA group.The model of middle cerebral artery occlusion (MCAO) was established by thread ligation.Neurological system symptoms were evaluated at 72 h after ischemia repeffusion.The histopathological changes of brain tissues were stained with hematoxylin and eosin (HE) and the platelet endothelial cell adhesion molecule-1 (CD31) expression was detected via immunohistochemistry.The markers of oxidation and inflammation including superoxide dismutase (SOD),malondialdehyde (MDA),tumor necrosis factor-α (TNF-α) and interleulin-1β (IL-1β) were examined.Results The symptoms of neurological injury in treatment groups were improved significantly compared with those in model group.The expressions of CD31 were increased,the activities of SOD and glutathione peroxidase (GSH-Px) were improved,and the levels of TNF-cα and IL-1β were decreased.Moreover,the most remarkable effect of treatment occurred in AST-Ⅳ and HSYA combination group.Conclusion AST-Ⅳ and HSYA in combination can exhibit obvious synergistic protective effects on ischemia reperfusion injury in rats,which is related to antiinflammation,anti-oxidation and angiogenesis pathway.