芪苈强心胶囊对心肌梗死大鼠心肌纤维化及TGF-β_1/Smad3信号通路的影响

Effect of Qili Qiangxin Capsule on myocardial fibrosis and TGF-β_1/Smad3 signaling pathway in rats with myocardial infarction

目的探讨芪苈强心胶囊对心肌梗死后大鼠心肌纤维化的影响及其作用机制。方法 SD雄性大鼠结扎冠脉左前降支,建立急性心肌梗死(Acute Myocardial Infarction,AMI)模型,4周后根据心脏超声结果随机分为模型组和芪苈强心组,另设假手术组,分别给予1 g/(kg·d)芪苈强心及等体积蒸馏水灌胃。4周后超声心动图检测大鼠心脏功能,取梗死周围心肌组织采用HE及Masson染色观察心肌病理形态改变,免疫组织化学方法检测心肌α-SMA表达,Western blotting方法检测心肌α-SMA、胶原Ⅰ(collagenⅠ)、转化生长因子-β_1(TGF-β_1)及p-Smad3蛋白表达。结果与假手术组比较,模型组左心室短轴缩短分数(FS)和射血分数(EF)明显降低(P<0.05),左心室收缩末期内径(LVIDs)和收缩末期容量(ESV)显著升高(P<0.05),心肌纤维化明显(P<0.05),α-SMA、collagenⅠ、TGF-β_1和p-Smad3等表达增加(P<0.05)。与模型组比较,芪苈强心组EF和FS明显升高(P<0.05),LVIDs和ESV明显降低(P<0.05),心肌纤维化程度减轻(P<0.05),α-SMA、collagenⅠ、TGF-β_1和p-Smad3等表达明显降低(P<0.05)。结论芪苈强心胶囊能够降低心肌梗死大鼠心肌纤维化程度,改善心脏功能,其作用机制可能与调控TGF-β_1/Smad3信号通路相关蛋白有关。

Objective To study the effect and mechanism of Qili Qiangxin Capsule（QQC） on myocar dial fibrosis of rats with myocardial infarction（MI）.Methods Acute myocardial infarction（AMI） model was induced by ligation of the proximal left anterior descending branch of coronary artery of SD male rats for four weeks.Then the survival rats with AMI were randomly divided into model group（n=12） or QQC group（n=9） according to the transthoracic echocardiography results,and 10 more rats were assigned into sham operation group.Rats of QQF group were intragastrically administered QQC at the dose of 1 g/kg once daily,while those of the other two groups took the same volume of distilled water,for consecutive four weeks.The cardiac function was measured using echocardiography,the myocardial tissue close to infarction was observed with HE or Masson staining,α-SMA expression in myocardial tissue was detected using immunohistochemistrical method,and protein expression of α-SMA,collagen I,transforming growth factor-β1（TGF-β1） and p-Smad3 were detected using Western blotting.Results Compared with the sham operation group,left ventricular fractional shortening（FS） and ejection fraction（EF） of model group were significantly lower（P〈0.05）,left ventricular end systolic diameter（LVID） and end systolic volume（ESV） increased significantly（P〈0.05）,myocardial fibrosis ratio was significantly higher（P〈0.05）,and the protein expression of α-SMA,collagenⅠ,TGF-β_1and p-Smad3 were higher（P〈0.05）.Compared with model group,EF and FS of QQF group were significantly lower（P〈0.05）,LVID and ESV were significantly higher（P〈0.05）,the degree of myocardial fibrosis was relieved,and α-SMA,collagenⅠ,TGF-β1,p-Smad3 protein expressions in myocardium were lower（P〈0.05）.Conclusion Qili Qiangxin Capsule was demonstrated to improve the cardiac function of rats with AMI by inhibiting the process of fibrosis remodeling,and the effects may be mediated through regulating TGF-β1/Smad3 signaling pathway.