青蒿素对大鼠心梗后交感神经重构的影响及其机制研究  

Effect of artemisinin on remodeling of sympathetic nerve and its mechanism of myocardial infarction rats

作　　者：郑武扬[1] 李卫华[1] 谢强[1] 黄峥嵘[1] 万晓群[1] 

机构地区：[1]厦门大学附属第一医院心血管内科,福建厦门361000

出　　处：《中国生化药物杂志》2015年第1期81-84,共4页Chinese Journal of Biochemical Pharmaceutics

摘　　要：目的研究青蒿素对大鼠心梗后交感神经重构的作用并探索其分子机制。方法 SD雄性大鼠70只,随机分成3组,假手术组10只,心梗组30只,心梗治疗组30只。开胸结扎冠状动脉左前降支制造心梗动物模型,术后24 h开始灌胃大鼠,心梗治疗组给予青蒿素75 mg/(kg·d),每天分3次灌胃,心梗组给予等剂量的0.5%羧甲基纤维素钠。假手术组开胸仅冠状动脉下穿线但不结扎,同时给予等剂量的0.5%羧甲基纤维素钠。治疗4周后,将动物处死并按需要取材。Masson染色法测量左室梗死面积,免疫组织化学定量分析梗死周边区生长相关蛋白(growth associated protein 43,GAP43)与酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性交感神经纤维的分布和密度及巨噬细胞数目,蛋白免疫印迹法检测梗死周边区IKBα、GAP43、TH、NGF等的表达。RT-PCR检测心肌组织炎症因子TNF-α和IL-1β的mRNA表达水平。结果心梗组与心梗治疗组心梗面积没有显著差异。心梗组GAP43和TH阳性交感神经纤维密度高于假手术组(P<0.05),心梗治疗组GAP43和TH阳性交感神经纤维密度低于心梗组(P<0.05)。心梗组TNF-α和IL-1β的mRNA高于假手术组(P<0.05),心梗治疗组炎症因子TNF-α和IL-1β的mRNA低于心梗组(P<0.05)。心梗组IKBα蛋白高于假手术组(P<0.05),心梗治疗组IKBα蛋白表达低于心梗组(P<0.05)。心梗组NGF、GAP43及TH蛋白的表达高于假手术组(P<0.05),心梗治疗组NGF、GAP43及TH蛋白的表达水平低于心梗组(P<0.05)。梗死组巨噬细胞数目比假手术组高,而心梗治疗组巨噬细胞数目低于心梗组(P<0.05)。结论青蒿素可以抑制心梗后交感神经重构,其机制可能是通过抑制心梗后炎症反应。Objective To study the effect of artemisinin on remodeling of sympathetic neural in rats with myocardial infarction and explore its molecular mechanism. Methods 70 SD male rats were randomly divided into three groups,10 rats in sham operation group,30 rats in myocardial infarction group,30 rats in MI administration group. The myocardial infarction model was induced by ligating the left anterior descending coronary artery. After 24 h,the rats in myocardial infarction administration group were gavage with artemisinin of 75 mg /（ kg·d）,three times a day,meanwhile,MI group received isodose 0. 5% of sodium carboxymethyl cellulose. Sham operation group were only opened chestcoronary artery under wear line but not ligation,while given isodose 0. 5% of sodium carboxymethyl cellulose. Four weeks after treatment,the rats were sacrificed and drawed materials according to the needs. Infarcted size of left ventricular were measured by Masson staining method. The growth associated protein in infarcted border zone（ GAP43）, distribution and density of tyrosine hydroxylase（ TH）-positive nerves, number of macrophages were quantitatively analysed by immunohistochemical method. IKB alpha,GAP43,TH and NGF in infarcted border zone were detected by Western blot. The inflammatory factor of TNF-α and IL-1 β mRNA expression level were detected by RT-PCR. Results There was no difference in myocardial infarction area between MI group and MI administration group. GAP43 and TH positive sympathetic nerve fibers density in MI group were higher than those in sham operation group,and the above indexes in MI administration group were lower than those in MI group（ P〈0. 05）. TNF-α and IL-1 β mRNA expression levels in MI group were higher than those in sham operation group,and the above indexes in MI administration group were lower than those in MI group（ P〈0. 05）. IKB α protein in MI group was higher than that in sham operation group,and the above indexes in MI administration group were lower than those in MI group（ P

关 键 词：青蒿素 交感神经重构 心肌梗死 

分 类 号：R541.7[医药卫生—心血管疾病]