失荅剌知丸及其拆方对局灶性脑缺血再灌注大鼠海马区细胞外信号调节蛋白激酶5通路的影响  

Effect of Shi-da-la-zhi-wan and its separate prescriptions on expression of ERK5 pathways in the hippocampus of focal cerebral ischemia reperfusion in rats

作　　者：王娜琳 左艳丽 李占涛 王佩佩 贾戌生 冯佳婷 马玉玮 贾孟辉 Wang Nalin;Zuo Yanli;Li Zhantao;Wang Peipei;Jia Xusheng;Feng Jiating;Ma Yuwei;Jia Menghui(College of Traditional Chinese Medicine of Ningxia Medical University,Yinchuan750004,China;不详)

机构地区：[1]宁夏医科大学中医学院,银川750004 [2]宁夏医科大学第二附属医院中医科

出　　处：《山西医药杂志》2020年第19期2555-2559,共5页Shanxi Medical Journal

基　　金：国家自然科学基金(81260568,81560816,81760906);宁夏回族自治区重点研发计划(2018BEG03078)。

摘　　要：目的探讨失荅剌知丸及其拆方对脑缺血再灌注损伤模型大鼠治疗中的作用机制及其可能的有效配伍成分。方法将204只SPF级SD雄性大鼠按随机数字表法随机分为空白对照组(A组),假手术组(B组),模型组(C组),失荅剌知丸组(D组),巴豆组(E组),巴豆+三药组(F组),巴豆+余药组(G组),其中后5组制备局灶性脑缺血再灌注模型,并按取材时间点不同分为1 d、3 d、7 d组。各组大鼠取材前应用Garcia JH法进行神经功能评分。应用HE染色法观察大鼠各时间点脑组织病理学形态改变;反转录聚合酶链反应(RT-PCR)法、蛋白质印迹法检测观察丝裂原活化蛋白激酶-细胞外信号调节蛋白激酶(MAPK-ERK)信号通路中ERK5的蛋白表达水平。结果与空白对照组及假手术组相比,各组神经功能评分评分均减低、p-ERK5活化程度均升高、ERK5的mRNA相对表达含量明显升高(P<0.01);与模型组相比,各药物组神经功能评分均增加、p-ERK5活化程度均升高、ERK5mRNA相对表达含量均升高(P<0.05或P<0.01);各药物组中,失荅剌知丸组神经功能评分、p-ERK5活化程度及ERK5的mRNA相对表达含量高于各拆方组,各拆方组中以巴豆+三药组神经功能评分、p-ERK5活化程度及ERK5的mRNA相对表达含量最高(P<0.05或P<0.01);模型组及各药物组神经功能评分、p-ERK5活化程度、ERK5的mRNA相对表达含量随时间延长而增加。HE染色结果现示模型组大鼠海马CA1区神经细胞较空白对照组及假手术组排列松散、紊乱、模糊,胞核与胞质界限欠清晰;与模型组相比,各药物组神经细胞形态改善明显;各药物组中以失荅剌知丸组改善效果最明显;各拆方组中以巴豆+三药组神经细胞形态改善较为明显。结论失荅剌知丸及各拆方组均可改善大鼠脑缺血再灌注后的神经功能损伤,抑制神经细胞凋亡,这可能与其参与调节MAPK-ERK通路中ERK5的表达相关;各拆方组中以巴豆、柴胡、黑诃子、Objective To explore the mechanism of action and possible effective components of Shi-da-la-zhi-wan and its separate prescriptions in the treatment of cerebral ischemia-reperfusion injury model rats.Methods Two hundred and four male SPF-grade Sprague-Dawley rats were randomly divided into blank control group(group A),sham operation group(group B),model group(group C),Shi-da-la-zhi-wan group(group D),croton group(group E),croton+three-drugs group(Group F),and croton+extra-drugs group(group G),and the last 5 groups were used to prepare focal cerebral ischemia reperfusion models.According to the different time points of material collection,they wer divided into 1d,3d and 7d groups.The neurological scores of the rats in each group were scored by Garcia JH method.HE staining was used to observe the pathological changes of brain tissue at various time points in rats.Western Blot and RT-PCR were used to observe the protein expression levels of ERK5.Results Compared with the blank control group and the sham operation group,the neurological function scores of each group were reduced,the p-ERK5 activation level was increased,and the relative expression level of ERK5 mRNA was significantly increased(P<0.01).Compared with the model group,the nerve function score of each drug group was increased,the activation degree of p-ERK5 was increased,and the relative expression level of ERK5 mRNA was increased(P<0.05 or P<0.01).Among the drug groups,the neurological score,p-ERK5 activation level and the relative expression level of ERK5 mRNA in the Shi-da-la-zhi-wan group were higher than those of the separate prescriptions groups.In the above experimental results,the croton+three-drugs group expressed best in all separate prescriptions groups(P<0.05 or P<0.01).The neurological function score,p-ERK5 activation level,and the relative expression level of ERK5 mRNA in the model group and each drug group increased with time.HE staining results showed that compared with the blank control group and the sham operation group,the neurons in the

关 键 词：失荅剌知丸 脑缺血再灌注 拆方 

分 类 号：R285.5[医药卫生—中药学]