通心络胶囊对异丙肾上腺素诱导的心肌肥厚大鼠心功能及心肌纤维化的影响

Effects of Tongxinluo Capsules on cardiac function and myocardial fibrosis in rats with isoproterenol-induced cardiac hypertrophy

目的探讨通心络胶囊(人参、全蝎、赤芍等)对异丙肾上腺素(ISO)诱导的心肌肥厚大鼠心功能及心肌纤维化的影响。方法雄性SD大鼠45只随机均分为对照组,ISO组和通心络组。通心络组给予连续28 d通心络灌胃,而ISO组和对照组则给予生理盐水。ISO组和通心络组连续7 d皮下注射ISO。治疗4周后,测量左心室收缩末期压力(LVESP)、左心室舒张末期压力(LVEDP)及左心室压力上升与下降最大速率(±dp/dtmax)的血流动力学指标;计算心脏质量指数(HWI)和左心室质量指数(LVWI);检测血清和心肌中氧化应激指标超氧化物歧化酶(SOD)和丙二醛(MDA)水平;采用酶联免疫吸附法检测血清与心肌组织NO水平;采用Masson染色观察心肌纤维化;RT-PCR检测心肌内皮型NO合酶(eNOS)mRNA表达量;Western blot法测定eNOS和磷酸化eNOS(p-eNOS)蛋白表达水平。结果与对照组相比,ISO组的LVESP及±dp/dtmax均减小,心肌纤维化明显,血清与心肌SOD和NO水平降低,心肌eNOS的mRNA和蛋白表达及p-eNOS的蛋白表达均明显减少,LVEDP、HWI、LVWI、血清和心肌MDA水平显著增加。与ISO组相比,通心络组LVESP及±dp/dtmax均增加,心肌纤维化程度减轻,血清及心肌SOD和NO水平均升高、心肌eNOS的mRNA和蛋白表达及p-eNOS的蛋白表达均增加,LVEDP、HWI、LVWI、血清和心肌MDA水平均显著减少。结论通心络胶囊可改善ISO诱导的心肌肥厚大鼠的心功能并减轻心肌纤维化,其机制可能与通心络胶囊激活eNOS/NO信号通路及抗氧化应激有关。

AIM To explore the effects of Tongxinluo（ TXL） Capsules（ Ginseng Radix et Rhizoma,Scorpio,Paeoniae Radix rubra,etc.） on cardiac function and myocardial fibrosis in rats with isoproterenol（ ISO）-induced cardiac hypertrophy. METHODS Forty-five male SD rats were randomly and equally divided into three groups,control group,ISO group and TXL group. Rats in the TXL group were consecutively intragastric administrated with TXL for twenty-eight days,and then received the hypodermic injection of ISO for seven days together with the control group,while rats in the control and ISO groups received normal saline. Four weeks after the treatment,the hemodynamic parameters,including left ventricular end systolic pressure（ LVESP）,left ventricular end diastolic pressure（ LVEDP）,maximum rate of pressure development（ ＋ dp / dtmax） and maximum rate of pressure decline（-dp /dtmax） were measured. The indexes of heart weight/ body weight and left ventricle weight/body weight,which were defined as heart weight index（ HWI） and left ventricle weight index（ LVWI）,respectively,were calculated. Masson＇s trichrome staining was used for evaluating myocardial fibrosis,oxidative stress for levels of malondialdehyde（ MDA） and superoxide dismutase（ SOD） in serum and tissue. The levels of nitric oxide（ NO） in serum and tissue were also measured by ELISA. The mRNA of endothelial NO synthase（ eNOS） was measured by RT-PCR. The protein expressions of eNOS and phosphorylation of eNOS（ p-eNOS） were detected by Western blot.RESULTS Compared with the control group,the LVESP and ± dp / dtmaxdeclined; myocardial fibrosis severed;levels of SOD and NO in serum and myocardium decreased; mRNA of eNOS and protein expressions of p-eNOS and eNOS reduced; LVEDP,HWI,LVWI and levels of MDA in serum and myocardium increased,in the ISO group.Compared with the ISO group,the TXL group improved LVESP and ± dp / dtmax; augmented levels of SOD and NO in serum and myocardium; increased mRNA of eNOS and protein expressions of p-eNOS and eNOS; however,reduced LVEDP,HWI,LVWI,degree of myocardial fibrosis and levels of MDA in serum and myocardium. CONCLUSION TXL Capsules can improve cardiac function and attenuate myocardial fibrosis in rats with ISO-induced cardiac hypertrophy. It indicates that eNOS / NO signal pathway and anti-oxidative stress may be involved in its mechanism.