丹参素与小鼠心脏中的内质网Ca^(2+)渗漏通道SEC61α相互调节心肌梗死后纤维化的作用  

Effects of Danshensu on myocardial fibrosis by interacting with endoplasmic reticulun Ca^(2+)leakage channel SEC61αin mouse heart

作　　者：刘俊雄 王毅 LIU Junxiong;WANG Yi(Department of Pharmacy,Gezhouba Central Hospital of Chinese Medicine,Hubei,Yichang 443002,China)

机构地区：[1]国药葛洲坝中心医院药学部,湖北省宜昌市443002

出　　处：《河北医药》2021年第12期1844-1847,共4页Hebei Medical Journal

基　　金：国家级自然科学基金项目(编号:81372998)。

摘　　要：目的观察丹参素通过对心肌梗死小鼠心脏中的内质网Ca^(2+)渗漏通道SEC61α的调控对其心肌纤维化的影响。方法清洁级C57BL/6小鼠随机分为4组,每组18只,分别为假手术组、模型组、卡托普利组和丹参组。其中模型组和药物处理组均经过冠状动脉闭塞手术建立心肌梗死小鼠模型,随后假手术组和模型组分别给予0.9%氯化钠溶液灌胃,药物处理组分别给予等量的卡托普利和丹参素处理。通过心脏超声和心重指数计算得到药物处理对小鼠心功能指标的影响;通过羟脯氨酸和心肌氧自由基、过氧化物等含量检测,观察小鼠心肌羟脯氨酸和氧化应激水平;通过组织切片后Masson染色和Western blot实验,对小鼠心肌胶原容积变化和其内质网核心蛋白SEC61α蛋白的相对表达水平。结果丹参素处理后,心肌梗死小鼠心功能指标LVESd、LVEDd均低于模型组(P<0.05),LVEF、LVFS均高于模型组(P<0.05);心重指数的计算结果显示丹参素可降低心肌梗死小鼠CWI;羟脯氨酸含量和SOD、MDA的测定结果发现,丹参素可降低心肌梗死小鼠羟脯氨酸和SOD活性,升高MDA水平(P<0.05);Masson染色后的结果显示丹参素可降低心肌组织的胶原容积分数(P<0.05);Western blot结果表明丹参素组小鼠的SEC61α蛋白相对表达水平均低于模型组(P<0.05)。结论丹参素可通过与小鼠心脏中的内质网Ca2+渗漏通道SEC61α相互作用降低心肌梗死小鼠的纤维化水平。Objective To investigate the effects of Danshensu on myocardial fibrosis by interacting with endoplasmic reticulun Ca^(2+)leakage channel SEC61αin mouse heart.Methods The clean grade C57BL/6 mice were randomly divided into four groups:sham operation group(n=18),model group(n=18),captopril group(n=18)and danshensu group(n=18).The mice in model group,captopril group and danshensu group were subjected to coronary occlusion surgery to establish a mouse model of myocardial infarction.Then the mice in sham operation group and model group were given 0.9%saline irrigation while those in drug-treated group were treated with same doses of captopril and danshensu,respectively.The effects of drug treatment on cardiac function indexes in mice were obtained through cardiac ultrasound and cardiac weight index calculation.The levels of hydroxyproline and oxidative stress in myocardium of mice were observed through the detection of hydroxyproline,myocardial oxygen free radicals and peroxides.The changes of the volume of myocardial collagen and the relative expression level of SEC61αprotein of the endoplasmic reticulum of mice were analyzed by Masson staining and Western Blot after tissue sectioning.Results After Danshensu treatment,the cardiac function indexes LVESd and LVEDd in myocardial infarction mice were significantly lower than those in model group(P<0.05),while LVEF and LVFS were significantly higher than those in model group(P<0.05).Moreover,the calculation results of heart weight index showed that Danshensu could reduce CWI in myocardial infarction mice.The content and the results of SOD and MDA suggested that danshensu could reduce the hydroxyproline and SOD activity of mice with myocardial infarction and increase the levels of MDA(P<0.05).In addition,Masson staining results showed that danshensu could reduce the collagen volume fraction of myocardial tissue(P<0.05).The results of Western blot showed that the relative expression levels of SEC61αprotein in danshensu group were significantly lower than those in model

关 键 词：丹参素 SEC61α 心肌梗死 心肌纤维化 

分 类 号：R542.22[医药卫生—心血管疾病]