马来酸依那普利对阿霉素诱导大鼠心力衰竭的治疗作用  

Therapeutic effects of enalapril maleate on doxorubicin-induced heart failure in rats

作　　者：黄姝彦 栾玉玲 张颖[1] 钱俊峰[1] 刘宗军[1] HUANG Shu-yan;LUAN Yu-ling;ZHANG Ying;QIAN Jun-feng;LIU Zong-jun(Department ofCardiology,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属普陀医院心内科,上海201203

出　　处：《中国临床药理学杂志》2024年第4期569-573,共5页The Chinese Journal of Clinical Pharmacology

基　　金：上海市普陀区卫健委优势学科基金资助项目(2019ysxk01,2023ysxk01);上海市普陀区卫健委科技创新基金资助项目(ptkwws202221)。

摘　　要：目的 基于丝裂原活化蛋白激酶(MAPK)信号通路,探究马来酸依那普利片对阿霉素导致的心力衰竭大鼠的治疗作用及其机制。方法 从40只雄性SD大鼠中随机选取11只作为正常组(等量0.9%NaCl),剩余29只用腹腔注射3 mg·kg^(-1)·w^(-1)阿霉素制备心力衰竭模型。造模成功后随机分为模型组15只和实验组14只。实验组灌胃给予1.8 mg·kg^(-1)·d^(-1)马来酸依那普利混悬液;正常组和模型组均灌胃给予等量0.9%NaCl。8周后,对各组大鼠行心脏彩超,记录各组左心室射血分数(LVEF),用酶联免疫吸附试验法检测血清心肌损伤指标水平,用实时荧光定量聚合酶链反应法和蛋白质印迹法检测MAPK信号通路相关mRNA和蛋白的表达水平。结果 正常组、模型组和实验组的LVEF值分别为(77.85±3.34)%、(41.39±2.87)%和(60.10±6.53)%,血清脑钠肽含量分别为(219.30±10.59)、(333.90±61.19)和(260.00±16.10)pg·mL^(-1),Mapk8ip2相对表达水平分别为1.00±0.01、2.60±0.12和2.00±0.08,Mapk8ip3相对表达水平分别为1.00±0.00、6.77±1.04和3.66±0.54,Mapk1相对表达水平分别为1.00±0.00、4.40±0.14和2.71±0.24,Mapk3相对表达水平分别为1.00±0.01、7.83±0.34和2.71±0.24,P38-MAPK蛋白相对表达水平分别为1.00±0.05、1.14±0.02和1.02±0.03,细胞外调节蛋白激酶1/2蛋白相对表达水平分别为1.00±0.07、1.49±0.03和1.16±0.10,c-Jun氨基末端激酶1/2蛋白相对表达水平分别为1.00±0.03、1.65±0.19和1.14±0.01;模型组的上述指标与实验组和正常组比较,在统计学上差异均有统计学意义(均P<0.01)。结论 马来酸依那普利片对心力衰竭大鼠有治疗作用,其机制可能是通过调控MAPK信号通路来实现的。Objective To investigate the therapeutic effects and mechanism of enalapril maleate tablet on doxorubicin-induced heart failure rats based on mitogen-activated protein kinase(MAPK)signaling pathway.Methods Eleven of the 40 male SD rats were randomly selected as the normal group(equivalent to 0.9% NaCl),and the remaining 29 were prepared with intraperitoneal injection of 3mg·kg^(-1)·w^(-1) doxorubicin to prepare heart failure model.After successful modeling,they were randomly divided into model group(n=15 cases) and experimental group(n=14 cases).Experimental group was given 1.8 mg·kg^(-1)·d^(-1) enalapril maleate suspension for gavage;normal and model groups were given the same amount of 0.9%NaCl by gavage.After 8 weeks,the rats were subjected to cardiac ultrasound,the left ventricular ejection fractions(LVEF) of each group were recorded,the serum myocardial injury index level was detected by enzyme-linked immunosorbent assay,and the expression levels of mRNA and protein related to the MAPK signaling pathway were detected by real-time quantitative polymerase chain reaction and Western blot.Results The LVEF values of control,model and experimental groups were(77.85±3.34%) %,(41.39±2.87%) % and(60.10±6.53%) %;serum brain natriuretic peptide contents were(219.30±10.59),(333.90±61.19) and(260.00±16.10) pg · mL^(-1);the relative expression levels of Mapk8ip2 were 1.00±0.01,2.60±0.12 and 2.00±0.08;the relative expression levels of Mapk8ip3 were 1.00±0.00,6.77±1.04 and3.66±0.54;the relative expression levels of Mapk1 were 1.00±0.00,4.40±0.14 and 2.71±0.24;the relative expression levels of Mapk3 were 1.00±0.01,7.83±0.34 and 2.71±0.24;the relative expression levels of P38-MAPK were 1.00±0.05,1.14±0.02 and 1.02±0.03;the relative expression levels of extracellular regulated protein kinase 1/2 protein were 1.00±0.07,1.49±0.03 and 1.16±0.10;the relative expression levels of c-Jun N-terminal kinase 1/2 protein were 1.00±0.03,1.65±0.19 and 1.14±0.01,respectively.Compared with the model group,the

关 键 词：马来酸依那普利片 阿霉素 心力衰竭 转录组测序 丝裂原活化蛋白激酶信号通路 

分 类 号：R972.4[医药卫生—药品]