黄茂甲昔对MCAO诱导的急性脑缺血再灌注损伤的保护作用  

Protective Effect of Astragaloside A on Acute Cerebral Ischemia Reperfusion Injury Induced by Middle Cerebral Artery Occlusion

作　　者：刘海超[1] 张晓芸 白晋[1] 张绿明[1] 王培福[1] LIU Haichao;ZHANG Xiaoyun;BAI Jin;ZHANG Lvming;WANG Peifu(Department of Neurology,Space Center Hospital Beijing,100049,China)

机构地区：[1]航天中心医院神经内科,北京市100049

出　　处：《医学分子生物学杂志》2019年第1期13-18,共6页Journal of Medical Molecular Biology

摘　　要：目的探索黄罠甲昔对脑缺血再灌注MCAO模型大鼠的治疗作用和机制。方法利用大脑中动脉闭塞(middle cerebral artery occlusion, MCAO)法制备大鼠脑缺血/再灌注(ischemia reperfusion, IR)损伤模型。SD大鼠随机分为4组:健康组(Ctrl);健康加药组(AA):健康大鼠腹腔注射黄英甲昔(astragalosideA, AA);模型组(MCAO);模型加药组(MCAO + AA)。苏木素伊红(HE)染色检测脑组织病理损伤情况;TUNEL染色检测脑组织细胞凋亡情况;免疫组化检测细胞间黏附分子-1(intercellular cell adhesionniolecule-l,ICAM-1)表达;E试剂盒检测血清氧化应激标记SOD、MDA、GSH水平;ELISA检测炎性因子IL-6, IL-18和IL-1β水平。蛋白免疫印迹检测NF-kB P65/p-p65、凋亡相关微粒蛋口( apoptosis-associatedspeck-like protein containing CARD, ASC)、Caspase-3 和 Caspase-9 表达情况;结果与 MCAO 组相比较,MCAO+AA组脑组织损伤程度明显减轻;细胞凋亡率明显减少(P<0.01);SOD和LDH水平明显增加(P<0.01),而MDA明显减少(P<0.01);炎性因子IL-6、IL-18、IL-1β水平明显减少(P<0.01);p-p65、ASC、Caspase-3和Caspase-9相对蛋白表达水平明显降低.结论黄英甲昔改善大鼠脑缺血再灌注氧化应激损伤,缓解免疫功能紊乱,可能成为治疗缺血再灌注损伤的潜在药物。Objective To explore the therapeutic effect of astragaloside A ( AA) on cerebral ischemia reperfusion (IR) injury and the underlying mechanism. Methods The rat model of cerebral IR injury was established by middle cerebral artery occlusion ( MCAO ). Sprague Dawley (SD) rats were randomly divided into four groups: healthy group, healthy + AA group, model group and model + AA group. In the control + AA group, healthy rats were injected intraperitoneally with AA, while the model rats were given intraperitoneal injection of AA also in the model + AA group. The pathological damage of the brain tissues was detected by hematoxylin-eosin ( HE) staining. The apoptosis of neurons was detected by TUNEL staining. The expression of intercellular adhesion molecule-1 (ICAM-1 ) was immunohistochemically detected. Serum oxidative stress markers superoxide dismutase ( SOD), malondialdehyde ( MDA ) and lactate dehydrogenase ( LDH ) were measured. ELISA was used to detect inflammatory cytokines IL-6 , IL-18 and IL-1β. The expression levels of apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)( ASC), caspase-3 and caspase-9 were detected by Western blotting. Results The damage of brain tissues, the apoptosis rate, SOD and LDH levels, levels of IL-6, IL-18 ancl IL-1β,relative expression levels of p-p65 , ASC, caspase-3 and caspase-9 were significantly reduced in model + AA group as compared with those in the model group. Conclusion Astragaloside A improves the oxidative stress injury of cerebral IR in rats, alleviates immune dysfunction, and it may become a potential drug for the treatment of IR injury.

关 键 词：脑缺血再灌注 黄罠甲昔 炎性小体 MCAO 氧化应激 

分 类 号：R743[医药卫生—神经病学与精神病学]