芪参益气汤对阿霉素致心力衰竭大鼠心功能及miR133a表达的影响

The Influence of Qishen Yiqi Decoction on Cardiac Function and miR133a Expression in Rats with Chronic Heart Failure Induced by Adriamycin

目的探讨芪参益气汤对阿霉素致心力衰竭(CHF)大鼠心功能及微小核糖核酸133a(miR133a)表达的影响。方法选取清洁级健康雄性Wistar大鼠90只,随机分为对照组、模型组、西药组及中药低、中、高剂量组,各15只。模型组、西药组及中药低、中、高剂量组采用阿霉素尾静脉注射建立CHF模型,对照组大鼠以等量0.9%氯化钠溶液尾静脉注射。模型建立后,模型组和对照组分别予以0.9%氯化钠溶液10mL/kg灌胃给药,每日1次;西药组予以0.25mg/mL卡托普利溶液10mL/kg灌胃给药每日1次;中药低、中、高剂量组分别予以0.8g/mL、1.6g/mL、3.2g/mL芪参益气汤10mL/kg,灌胃给药,每日1次。各组大鼠均给药28d。检测比较各组心脏功能、心肌细胞凋亡指数(AI)、心肌组织B淋巴细胞瘤-2(Bcl-2)蛋白、含半胱氨酸的天冬氨酸蛋白水解酶-9(Caspase-9)表达水平及miR133a、Bcl-2mRNA、Caspase-9mRNA表达水平。结果与模型组比较,其他各组大鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)较低,心肌AI较低,心肌组织Caspase-9蛋白及Caspase-9mRNA表达水平较低,且除LVEDD指标中药中剂量组与中药低剂量组比较差异无统计学意义之外,其余指标均中药低剂量组>中药中剂量组>中药高剂量组和西药组,差异均有统计学意义(P<0.05)。与模型组比较,其他各组大鼠射血分数(EF)、短轴缩短分数(FS)较高,心肌组织Bcl-2蛋白及miR133a、Bcl-2mRNA表达水平较高,且中药低剂量组<中药中剂量组<中药高剂量组和西药组,差异有统计学意义(P<0.05)。结论芪参益气汤能明显改善CHF大鼠的心功能,而且剂量越高效果越好,其作用可能与促进miR133a表达,调节miR133a下游Bcl-2、Caspase-9蛋白表达水平,抑制心肌细胞凋亡有关。

Objective To analysis the influence of Qishen Yiqi decoction on cardiac function and microRNA 133a(miR133a)expression in rats with chronic heart failure(CHF)induced by adriamycin.Methods Ninety male Wistar rats were randomly divided into the control group,model group,western medicine group,and Chinese medicine low-dose group,medium-dose group and high-dose group,n=15 for each group.CHF model were establ:shed by adriamycin injection into tail vein.Rats in the control group was received equivalent 0.9%sodium chloride solution injection into tail vein.After the model was established,the model group and control group were gavaged 0.9%sodium chloride solution 10 mL/kg.The western medicine group was gavaged 0.25 mg/mL captopril solution 10 mL/kg.The Chinese medicine low-dose group,medium-dose group and high-dose group were gavaged 0.8 g/mL,1.6 g/mL,3.2 g/mL Qishen Yiqi decoction 10 mL/kg.All rats in each group were treated for 28 d.The cardiac function,myocardial apoptosis index(AI),expression of B lymphocytic tumor-2(Bcl-2)protein and cysteine containing aspartate protein hydrolase-9(caspase-9)and miR133a,Bcl-2 mRNA,Caspase-9 mRNA in myocardial tissue were compared between groups.Results Compared with the model group,left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVESD),myocardial AI,Caspase-9 and Caspase-9 mRNA in myocardial tissue were decreased in each group,and the Chinese medicine low-dose group Chinese medicine medium-dose group Chinese medicine high-dose group,and western medicine group(P<0.05).Compared with the model control group,ejection fraction(EF)and short axis shortening fraction(FS),Bcl-2 protein,miR133a,and Bcl-2 mRNA in myocardial tissue were increased in each group,and Chinese medicine low-dose group Chinese medicine medium-dose group Chinese medicine high-dose group and western medicine group(P<0.05).Conclusion Qishen Yiqi Decoction could significantly improve cardiac function in CHF rats,and the higher the dose,the better the effect.The influence was related to promote miR133a,regulate the expression of Bcl-2 and Caspase-9 protein downstream of miR133a,and inhibit cardiomyocyte apoptosis.