苦参素注射液改善阿霉素所致慢性心力衰竭大鼠心功能和心室重构的作用及机制  

Effect and mechanism of oxymatrine injection improves cardiac function and ventricular remodeling in adriamycin induced chronic heart failure rats

作　　者：叶海峰[1] 曹旭丹[1] YE Haifeng;CAO Xudan(Department of Cardiovascular Surgery,Handan Central Hospital,Handan,Hebei 056001,China)

机构地区：[1]邯郸市中心医院心血管外科,河北省邯郸市056001

出　　处：《中国动脉硬化杂志》2023年第9期762-770,共9页Chinese Journal of Arteriosclerosis

基　　金：河北省医学科学研究课题(20220550)。

摘　　要：[目的]探讨苦参素注射液(OMT)对阿霉素所致慢性心力衰竭(CHF)大鼠心功能和心室重构的影响及可能机制。[方法]采用腹腔注射(ip)阿霉素(1.5 mg/kg, 2次/周,共6周)的方法构建CHF大鼠模型,设模型组、卡托普利注射液(CTP,6.5 mg/kg)组和OMT低(25 mg/kg)、中(50 mg/kg)、高(100 mg/kg)剂量组;另设对照组,每组10只。各组分别每天1次腹腔注射给药4周后,通过小动物超声成像系统检测心功能指标[左心室收缩期末内径(LVESD)、左心室舒张期末内径(LVEDD)、短轴缩短率(LVFS)、射血分数(LVEF)、每搏输出量(SV)],酶联免疫吸附法(ELISA)检测血清心肌肌钙蛋白I(cTnI)、脑钠肽(BNP)、基质裂解素2(ST2)含量,计算左心室肥厚指数(LVHI),HE染色和Masson染色观察心肌组织形态变化和纤维化状况,Western blot法检测胶原蛋白Ⅰ(Coll-1)、α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、Smad2、p-Smad2、Smad3、p-Smad3、Smad7蛋白表达。[结果]与模型组比较,CTP组和OMT低、中、高剂量组大鼠LVESD和LVEDD分别降低,LVFS、LVEF和SV分别升高(均P<0.05),cTnI、BNP和ST2含量以及LVHI分别降低(均P<0.05),心肌组织形态病理性改变和纤维化状况明显改善,胶原容积分数(CVF)分别降低(均P<0.05),Coll-1、α-SMA和TGF-β1表达量分别降低,p-Smad2/Smad2比值和p-Smad3/Smad3比值分别下降,Smad7相对表达量分别升高(均P<0.05)。OMT对CHF大鼠各指标的影响具有剂量依赖性,且OMT高剂量组对各指标的影响明显优于CTP组。[结论] OMT具有改善CHF大鼠心功能、抑制心室重构的作用,其作用机制可能与抑制TGF-β1/Smads信号通路有关。Aim To investigate the effect and possible mechanism of oxymatrine injection(OMT)on cardiac function and ventricular remodeling in doxorubicin-induced chronic heart failure(CHF)rats.Methods The rat model with CHF was established by intraperitoneal injection(ip)of adriamycin(1.5 mg/kg,twice a week for 6 weeks).The model group,captopril injection(CTP,6.5 mg/kg)group and OMT low(25 mg/kg),medium(50 mg/kg),high(100 mg/kg)dose group were set up,and the control group was set up,with 10 rats in each group.The rats in each group were treated by intraperitoneal injection once a day.4 weeks later,the cardiac function indexes(left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular fractional shortening(LVFS),stroke volume(SV))were measured through animal ultrasound;the content of cardiac troponin I(cTnI),brain natriuretic peptide(BNP),stromelysin-2(ST2)in serum were detected by enzyme-linked immunosorbent assay(ELISA);the left ventricular hypertrophy index(LVHI)was calculated;the morphological changes and fibrosis of myocardial tissue were observed by HE staining and Masson staining;the expression of collagen I(Coll-1),αsmooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),Smad2,p-Smad2,Smad3,p-Smad3,Smad7 were detected by Western blot.Results Compared with the model group,the LVESD and LVEDD were decreased in CTP group and OMT low,medium,high dose groups;the LVFS,LVEF and SV were increased(all P<0.05).The contents of cTnI,BNP and ST2 were decreased(all P<0.05).The pathological changes and fibrosis of myocardial tissue were significantly improved,and the collagen volume fraction(CVF)were decreased(P<0.05).The expressions of Coll-1,α-SMA and TGF-β1 were decreased;the ratio of p-Smad2/Smad2 and p-Smad3/Smad3 were decreased;the expression of Smad7 were increased(all P<0.05).The effect of OMT on various indexes of CHF rats were dose-dependent,and the effect of OMT high-dose group on various indexes were significantly better than those of CTP group.Conclusion

关 键 词：慢性心力衰竭 苦参素注射液 心功能 心室重构 TGF-β1/Smads信号通路 

分 类 号：R541.6[医药卫生—心血管疾病]