心悦胶囊对心脏肥大大鼠甘油磷脂代谢酶表达的影响  

Effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in a rat model of cardiac hypertrophy

作　　者：张浩 丁小云 王虎 李停停 邱雨美 谢梦蝶 董伟 沈亦欣 汤喜兰 ZHANG Hao;DING Xiao-yun;WANG Hu;LI Ting-ting;QIU Yu-mei;XIE Meng-die;DONG Wei;SHEN Yi-xin;TANG Xi-lan(School of Pharmacy,Jiangxi Science&Technology Normal University,Nanchang 330013,China;Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Jiangxi Provincial Key Laboratory of Drug Design and Evaluation,Nanchang 330013,China)

机构地区：[1]江西科技师范大学药学院,江西南昌330013 [2]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [3]江西省药物分子设计与评价重点实验室,江西南昌330013

出　　处：《中成药》2024年第11期3594-3602,共9页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(81960732,82360787);江西省自然科学基金项目(20224BAB206111);江西省卫生健康委员会(202311141);江西省药物分子设计与评价重点实验室开放课题(JKLDE-KF-2101);江西科技师范大学大学生创新创业训练计划项目(20231704203)。

摘　　要：目的探讨心悦胶囊对异丙肾上腺素(ISO)诱导的大鼠心脏组织和大鼠乳鼠原代心肌细胞中甘油磷脂代谢酶表达的影响。方法SD大鼠随机分为正常组、模型组、心悦胶囊干预组和心悦胶囊对照组,每组8只。采用腹腔注射ISO(30 mg/kg)连续14 d建立大鼠心脏肥大模型,造模前3 d预先灌胃0.393 g/kg心悦胶囊,每天给药1次直至实验结束。末次给药后,腹主动脉取血,取心脏并分离左、右心室,测定大鼠心脏指数、左心室指数、右心室指数;HE染色观察大鼠心肌组织病理形态学变化;RT-qPCR法检测心肌组织中心脏肥大相关胚胎基因ANP、β-MHC、α-SKA mRNA表达;生化法检测血清TC、TG、LDL-C、HDL-C水平。体外实验采用ISO 1μmol/L作用24 h诱导大鼠乳鼠心肌细胞肥大模型。通过检测心肌细胞面积、心脏肥大相关胚胎基因和心肌细胞蛋白含量,考察心悦胶囊12.5μg/mL对ISO诱导的心肌细胞肥大的影响。为进一步探索心悦胶囊抗心脏肥大的作用机制,采用RT-qPCR和Western blot法检测各组左心室组织和心肌细胞中甘油磷脂代谢酶Ⅵ组磷脂酶A_(2)(PLA2G6)、磷脂酶A_(1)成员A(PLA1A)、卵磷脂胆固醇酰基转移酶(LCAT)的基因和蛋白表达。结果体内实验结果显示,与正常组比较,模型组大鼠心脏指数、左心室指数、右心室指数、左心室心肌细胞横截面积均增加(P<0.05),左心室ANP、β-MHC、α-SKA mRNA表达和PLA2G6、PLA1A、LCAT mRNA及蛋白表达均升高(P<0.05),血清TC、TG、LDL-C水平升高(P<0.05),HDL-C水平降低(P<0.05);而心悦胶囊干预后抑制了上述指标的变化(P<0.05)。体外实验结果表明,心悦胶囊抑制了ISO诱导的心肌细胞表面积的增大,心肌细胞蛋白水平的升高,ANP、β-MHC、α-SKA mRNA表达的升高,以及PLA2G6、PLA1A、LCAT mRNA及蛋白表达的升高(P<0.05)。结论心悦胶囊能改善ISO诱导的大鼠心脏肥大,其作用机制与其调节甘油磷脂代谢相关酶PLA2G6、PLA1A、LAIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC andα-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A_(2)(PLA2G6),phospholipase A_(1) member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and

关 键 词：心悦胶囊 心脏肥大 异丙肾上腺素 脂质代谢 甘油磷脂代谢酶 

分 类 号：R285.5[医药卫生—中药学]