益母草碱对心肌重构大鼠ACE2、AngⅡ及Ang1-7的影响研究

Effects of Leonurine on ACE2,AngⅡ and Ang1-7 in rats with myocardial remodeling

目的观察益母草碱对心肌重构大鼠血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及血管紧张素1-7(angiotensin 1-7,Ang1-7)的影响,并探讨可能涉及的机制。方法以异丙肾上腺素(5 mg/kg/d)连续2周腹腔注射诱导大鼠心肌重构模型,在此基础上给予ACE2内源性激动剂乙酰甘氨酸重氮氨苯脒(diminazene aceturate,DIZE)(15 mg/kg/d)及低、中、高剂量益母草碱(7.5 mg/kg/d、15 mg/kg/d、30 mg/kg/d)干预治疗2周。治疗结束后以心脏超声检测各组实验动物左室舒张末期内径(left ventricular end diastolic dimension,LVEDd)、左室收缩末期内径(left ventricular end systolic dimension,LVEDs)、左室短轴缩短率(fractional shortening,FS)、射血分数(ejection fraction,EF);酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测各组动物血清及心肌组织ACE2、AngⅡ、Ang1-7的浓度;HE染色和Masson染色观察心肌重构病理学改变;免疫组织化学法观察各组大鼠左心室肌组织结缔组织生长因子(connective tissue growth factor,CTGF)、纤维连接蛋白(fibronectin,FN)蛋白质的表达水平。结果与模型组比较,高剂量益母草碱明显降低心肌重构大鼠LVEDd、LVEDs值及提高FS%、EF%值;明显改善大鼠左心室心肌重构病理改变;抑制左心室肌组织CTGF、FN蛋白质的表达水平及减少心肌胶原容积分数(collagen volume fraction,CVF);减少血清及左心室肌组织中AngII的浓度,及升高血清及左心室肌组织中ACE2、Ang1-7的浓度,差异均有统计学意义(P<0.05)。结论高剂量益母草碱(30 mg/kg/d)可改善异丙肾上腺素诱导的大鼠心肌重构,其机制可能与提高ACE2、Ang1-7的浓度有关。

Objective To observe the effects of leonurine on angiotensin converting enzyme 2(ACE2), angiotensin Ⅱ(AngⅡ) and angiotensin 1-7(Ang1-7) in rats with myocardial remodeling as well as to explore the possible mechanisms of above. Methods Isoproterenol(5 mg/kg/d) was injected intraperitoneally for 2 weeks to induce a model of myocardial remodeling in rats, then an ACE2 activator diminazene aceturate(DIZE)(15 mg/kg/d)and low, medium and high doses of leonurine(7.5 mg/kg/d,15 mg/kg/d, 30 mg/kg/d)were used on intervention therapy for 2 weeks. Cardiac ultrasound was used to detect left ventricular end diastolic dimension(LVEDd), left ventricular end systolic dimension(LVEDs), fractional shortening(FS) and ejection fraction(EF) of all the experimental animals. Method of ELISA was used to detect the concentration of ACE2, AngⅡ and Ang1-7 in both serum and myocardial tissues of the rats. Methods of HE staining and Masson staining were used to observe the pathological changes of myocardial remodeling. Immunohistochemical method was used to observe the protein expression levels of connective tissue growth factor(CTGF) and fibronectin(FN) in left ventricular myocardium. Results In the rats of high-dose group of leonurine, compared with the model group, LVEDd and LVEDs were significanly reduced(P<0.05) whereas FS% and EF% values were increased(P<0.05). The myocardial remodeling was obviously improved. Also the concentration of AngⅡ in serum and left ventricular myocardium was reduced(P<0.05)while that of ACE2 and Ang1-7 was increased(P<0.05). Conclusion High dose of leonurine(30 mg/kg.d) can improve Isoproterenol-induced myocardial remodeling in rats, and the mechanism could be related to the increase of the concentration of ACE2 and Ang1-7.