吴茱萸次碱改善压力超负荷所致大鼠左心结构及功能异常

摘要

目的 观察吴茱萸次碱(rutaecarpine,Rut)对压力超负荷所致大鼠左心室结构及功能的影响.方法 通过腹主动脉缩窄术(abdominal aortic constriction,AAC)制作心肌肥厚模型,造模4周后,随机分为AAC组、吴茱萸次碱低、高剂量组(10、20 mg/kg/d,po)和假手术(Sham)组.连续给药4周后测量大鼠尾动脉血压,并利用高分辨率小动物超声系统检测大鼠心脏结构和功能改变;分离组织计算左心室肥厚指数(LVHI);H&E染色观察左室心肌组织形态学变化;qRT-PCR法检测心肌心房钠尿肽(atrial natriuretic peptide,ANF) mRNA表达.结果 与Sham组比较,AAC大鼠血压明显升高(P＜0.05),LVHI显著增加;超声结果显示左室前壁(LVAW)和后壁(LVPW)厚度均大于Sham组(P＜0.05);而收缩及舒张期左室内径(LVID)低于Sham组;心功能指标左心室收缩末期心室容积(LV Vol.s)及舒张末期心室容积(LV Vol.d)和每搏输出量(SV)小于Sham组(P ＜0.05,P＜0.01),表明左室肥厚且收缩与舒张功能出现异常.H&E染色显示AAC组心肌细胞排列紊乱且细胞间隙增宽,伴有肌丝部分断裂;心肌组织ANF mRNA表达明显增加;给予吴茱萸次碱低、高剂量治疗后,血压显著降低(P＜0.05),LVHI明显减小;收缩期及舒张期LVAW及LVPW显著下降(P ＜0.05,P＜0.01),同时收缩及舒张期LVID和LV Vol.及SV的值增大(P ＜0.05,P＜0.01),表明吴茱萸次碱可有效改善左心室结构和心肌收缩舒张功能障碍;H&E染色观察发现心肌细胞排列趋于整齐且细胞间隙缩窄,未见明显肌丝断裂;同时下调心肌ANF mRNA水平的表达(P＜0.05).结论 吴茱萸次碱可显著改善腹主动脉缩窄术所致大鼠左室结构及心功能损害.%Objective To evaluate the efficacy of rutaecarpine (Rut)on left cardiac structure and function in rats with myocardial hypertrophy induced by pressure overload.Methods A rat model of myocardial hypertrophy was induced by abdominal aortic constriction(ACC).Rats were randomly divided into four groups:Sham group,AAC group,low dose (10 mg/kg,p.o.) of Rut group (Rut-L) and high dose (20 mg/kg,p.o.) of Rut group (Rut -H).The blood pressure of tail artery was measured before and after Rut treatment.The cardiac structure and function were detected by high resolution ultrasound imaging system (HRUIS).The myocardial pathology was examined by H&E staining.The left ventricular hypertrophy index(LVHI) was calculated.The level of atrial natriuretic peptide(ANF) mRNA was detected by qRT-PCR.Results The blood pressure was significantly increased in ACC group.HRUIS revealed that ACC increased systolic and diastolic left ventricular anterior wall(LVAW) thickness,left ventricular posterior wall (LVPW)thickness,left ventricular internal diameter(LVID) and average cardiac stroke volume(SV).Also,ACC increased LVHI and disorganized cardiomyocytes with widening of cell gap and partial rupture of muscle fibers,and increased ANF mRNA.After Rut treatments,AAC-elevated blood pressure was decreased,the LVID was narrowed,and the LVAW,LVPW and LVHI were decreased,while the LV Vol.and SV were increased.Cardiomyocyte hypertrophy was improved and the elevated ANF returned towards the normal level.Conclusion Rut could improve the AAC-induced left cardiac structure changes and function damage in rats.