摘要
目的:研究乌参醒脑方(Wushen-Xingnao,WSXN)对缺血性脑卒中大鼠的神经再生作用及其机制。方法:雄性Sprague Dawley(SD)大鼠接受大脑中动脉梗塞手术(middle cerebral artery occlusion,MCAO),灌胃乌参醒脑方提取物(30,60和120 mg·kg-1),观察记录各组动物神经行为学评分,采用外源性标记物5’-溴脱氧尿嘧啶核苷(5’-bromodeoxyuridine,5’-BrdU)和神经元核抗原(neuronal nuclear antigen,NeuN)进行免疫荧光标记检测梗死侧脑组织新生神经元细胞,试剂盒测定脑组织中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧物酶(glutathione peroxidase,GSH-Px)、丙二醛(malondialdehyde,MDA)含量,免疫印迹法检测梗死侧脑组织B淋巴细胞瘤-2蛋白(B-cell lymphoma-2,Bcl-2)、半胱氨酸蛋白酶(Caspase-3)蛋白表达水平。结果:乌参醒脑方能显著改善神经行为学缺陷,降低MCAO模型大鼠脑组织MDA的含量,提高脑组织SOD和GSH-PX的活性,并显著增加梗死侧脑组织皮层区BrdU+/NeuN+阳性细胞的数目,并呈剂量依赖性。上调抗凋亡蛋白Bcl-2表达水平,下调促凋亡蛋白Caspase-3表达水平。结论:乌参醒脑方能促进MCAO模型大鼠神经再生,该作用可能与其增加脑组织中抗氧化酶的活性、降低脂质过氧化水平、抑制神经细胞凋亡有关。
Objective: The nerve regeneration effects of Wushen-Xingnao Fang( WSXN) on middle cerebral artery occlusion( MCAO)-induced ischemic stroke in rats and its mechanism were studied. Methods: Male SpragueDawley( SD) rats were subjected to MCAO to simulate ischemic stroke. Rats were intragastrically administered with WSXN extract,neurobehavioral scores were recorded,and immunofluorescence labeling was performed with exogenous markers( 5 ’-bromodeoxyuridine,5 ’-BrdU) and neuronal nuclear antigen( NeuN) in the rats. The contents of superoxide dismutase( SOD),glutathione peroxidase( GSH-Px) and malondialdehyde( MDA) in the rat brain tissue were determined. The expressions of B-cell lymphoma-2( Bcl-2) and Caspase-3 protein in the infarcted brain tissue were detected by Western blotting. Results: In MCAO-induced ischemic rats,WSXN( 30,60,120 mg·kg-1) markedly improved the neurobehavioral scores of the rats and increased the number of BrdU+/NeuN+positive cells in the rat cerebral cortex in a dose-dependent manner. The content of MDA was significantlydecreased,and the content of SOD and GSH-PX activity were significantly increased in the rat brain tissue. In addition,WSXN up-regulated the expression of anti-apoptotic protein Bcl-2,and down-regulated the expression of pro-apoptotic protein Caspase-3. Conclusion: Wushen-Xingnao fang has nerve regeneration effect in rats with MCAO-induced ischemic stroke. Its mechanism may be attributed to the increase of antioxidation capacity,decrease of lipid peroxidation and inhibition of neuronal apoptosis.
作者
李育平
黄亿健
王虹
梁文意
贝伟剑
郭姣
LI Yu-ping;HUANG Yi-jian;WANG Hong;LIANG Wen-yi;BEI Wei-jian;GUO Jiao(Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine,Institute of Chinese Medicinal Science,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第8期922-927,共6页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81473588)
广东省重大科技专项资助项目(2013A022100041)
广东省联合培养研究生示范基地项目(20161315)
广药大“药创未来”众创空间建设
2017年中央支持地方高校发展专项资助项目(201708)。
关键词
乌参醒脑方
大脑中动脉梗塞模型
缺血性脑卒中
神经再生
Wushen-Xingnao Fang
middle cerebral artery occlusion model
ischemic stroke
nerve regeneration