川芎嗪对扩张型心肌病大鼠左心收缩功能的影响及机制  

Effect of Ligustrazine on left ventricular systolic dysfunction in dilated cardiomyopathy rats and its mechanism

作　　者：刘峰 刘华东 吴美善 林耀望 董少红 熊玮 LIU Feng;LIU Hua⁃dong;WU Mei⁃shan;LIN Yao⁃wang;DONG Shao⁃hong;XIONG Wei(Department of Cardiology,Shenzhen People′s Hospital,Shenzhen,Guangdong 518020;Department of Emergency,Longhua Hospital Affiliated Shenzhen People′s Hospital,Shenzhen,Guangdong 518109,China)

机构地区：[1]深圳市人民医院心血管内科,广东深圳518020 [2]深圳市人民医院龙华分院急诊科,广东深圳518109

出　　处：《热带医学杂志》2020年第5期625-629,共5页Journal of Tropical Medicine

基　　金：深圳市科技创新课题(JCYJ20160422151912249)。

摘　　要：目的探讨川芎嗪(LTZ)对扩张型心肌病(DCM)大鼠左心收缩功能的影响及机制。方法通过腹腔注射阿霉素(2.5 mg/kg,2次/周,共4周)建立大鼠扩张型心肌病模型(DCM组);LTZ组在建立大鼠扩张型心肌病模型的同时经过腹腔注射LTZ(100 mg/(kg·d),连续4周);白藜芦醇(RES)组在建立大鼠扩张型心肌病模型的同时经过腹腔注射RES(20 mg/(kg·d),连续4周)。采用心脏超声检查舒张期室间隔厚度(IVSd)、舒张期左室内径(LVEDd)、舒张期左室后壁厚度(LVPWd)、左心室射血分数(LVEF);HE染色观察心肌组织形态;ELISA法检测血清氨基末端脑钠肽前体(NTproBNP)、白细胞介素-1β(IL⁃1β)、肿瘤坏死因子-α(TNF⁃α)、转化生长因子-β1(TGF⁃β1)水平;Real time PCR和蛋白印迹法检测心肌组织癌胚抗原相关细胞粘附分子1(CEACAM1)、p⁃p38蛋白(p⁃p38 MAPK)、caspase 3表达情况。结果与正常组(Sham)大鼠相比,DCM组大鼠左心明显扩大,LVEF降低,血清NTproBNP、IL⁃1β、TNF⁃α水平增加,TGF⁃β1水平下降,心肌组织中CEACAM1、caspase 3、p⁃p38 MAPK的mRNA和蛋白表达水平增加,差异均有统计学意义(P<0.05);与DCM组大鼠相比,LTZ组大鼠心脏扩大明显减轻,LVEF上升,血清NTproBNP、IL⁃1β、TNF⁃α水平下降,TGF⁃β1水平增加,心肌组织中CEACAM1、caspase3、p⁃p38 MAPK的mRNA和蛋白表达水平下降,差异均有统计学意义(P<0.05);与DCM组大鼠相比,RES组大鼠心脏扩大更加明显,LVEF下降,血清NTproBNP、IL⁃1β、TNF⁃α水平上升,TGF⁃β1水平降低,心肌组织中CEACAM1、caspase3、p⁃p38 MAPK的mRNA和蛋白表达水平增加,差异均有统计学意义(P<0.05)。结论CEACAM1参与了扩张型心肌病的发生。川芎嗪可能通过降低CEACAM1的表达改善扩张型心肌病大鼠的左心收缩功能。Objective To investigate the effect of Ligustrazine(LTZ)on dilated cardiomyopathy(DCM)and its mechanisms.Methods The rats with DCM were established by intraperitoneally injecting adriamycin(2.5 mg/kg)twice a week for 4 weeks.The LTZ rats were intraperitoneally injected with adriamycin(2.5 mg/kg,twice a week)as well as LTZ(100 mg/kg·d)for 4 weeks.The Resveratrol(RES)rats were intraperitoneally injected with adriamycin(2.5 mg/kg,twice a week)as well as RES(20 mg/kg·d)for 4 weeks.Echocardiography was employed to invesigate the left ventricular end⁃diastolic diameter(LVEDd),interventricular septum thickness diameter(IVSd),left ventricular posterior wall thickness diameter(LVPWd)and left ventricular ejection fraction(LVEF).HE staining was performed to evaluate myocardial tissue.ELISA was performed to investigate the serum levels of N terminal pro B type natriuretic peptide(NTproBNP),interleukin⁃1β(IL⁃1β),tumor necrosis factor⁃α(TNF⁃α)and transforming growth factor⁃β1(TGF⁃β1).The mRNA and protein levels of carcinoembryonic antigen⁃related cell adhesion molecule 1(CEACAM1),caspase 3 and phosphorylated p38 mitogen⁃activated protein kinases(p⁃p38 MAPK)were detected by Real time PCR and Western bloting.Results Compared with those in the normal group(Sham)rats,the left heart of DCM group rats was enlarged;LVEF was decreased;serum levels of NTproBNP,IL⁃1β,TNF⁃αwere increased;TGF⁃β1 was decreased,and mRNA and protein expression of CEACAM1,caspase3,p⁃p38 MAPK in myocardium were increased,the differences were statistically significant(P<0.05).Compared with those in DCM rats,the LTZ group rats cardiac size was significantly decreased;LVEF was increased;serum levels of NTproBNP,IL⁃1β,TNF⁃αwere dereased;TGF⁃β1 was increased;the mRNA and protein levels of CEACAM1,caspase3,p⁃p38 MAPK in myocardium were decreased;the differences were statistically significant(P<0.05).Compared those in DCM group rats,the RES group rat showed more significantly expanded cardiac size;LVEF was decreased;s

关 键 词：川芎嗪 扩张型心肌病 CEACAM1 

分 类 号：R541[医药卫生—心血管疾病]