丹酚酸A对阿霉素诱导的心力衰竭大鼠心肌纤维化影响及机制研究

Myocardial Fibrosis in Rats with Congestive Heart Failure Induced by Adriamycin and Its Mechanism

目的:探讨丹酚酸A对阿霉素诱导的心力衰竭大鼠心肌纤维化的影响。方法:实验动物为由南昌大学实验动物中心提供的SPF级8周龄健康雄性SD大鼠30只。将大鼠随机分为大鼠阴性对照组(n=6),阳性对照组(n=6),低剂量治疗组(n=6)、中剂量治疗组(n=6)、高剂量治疗组(n=6),比较干预后两组大鼠心脏功能、生化指标及Galectin-3和TGF-β/Smads蛋白表达情况,统计干预后各组心肌细胞凋亡率,并观察干预后各组心肌组织病理形态学变化情况。结果:干预后阴性对照组与高剂量治疗组左心室等容收缩期压力升高最大速率(dp/dt max)、左心室收缩期压力下降最大速率(dp/dt min)、左室射血分数(LVEF)和左室舒张末压(LVEDP)水平均高于中剂量治疗组、低剂量治疗组、阳性对照组(P<0.05),左室收缩压(LVSP)水平均低于中剂量治疗组、低剂量治疗组、阳性对照组(P<0.05)。干预后阴性对照组与高剂量治疗组TNF-α、Hcy和ET水平均低于中剂量治疗组、低剂量治疗组、阳性对照组(P<0.05)。干预后阴性对照组与高剂量治疗组Galectin-3和TGF-β/Smads蛋白表达水平均低于中剂量治疗组、低剂量治疗组、阳性对照组(P<0.05)。高剂量治疗组与阴性对照组大鼠心肌细胞凋亡率均低于中剂量治疗组、低剂量治疗组、阳性对照组(P<0.05)。结论:针对心力衰竭心肌纤维化大鼠,使用大剂量丹酚酸A治疗,可有效改善心脏功能,抑制炎症反应,降低机体同型半胱氨酸和内皮素水平,减少细胞凋亡,进而达到抑制心肌纤维化的目的。

Objective:To investigate the effect of Salvianolic Acid A on myocardial fibrosis in rats with congestive heart failure induced by Adriamycin.Method:The experimental animals were 30 healthy male SD rats of SPF grade 8-week-old provided by the experimental animal center of Nanchang University.The rats were randomly divided into negative control group(n=6),positive control group(n=6),low-dose treatment group(n=6),middle-dose treatment group(n=6)and high-dose treatment group(n=6).The cardiac function,biochemical indexes,protein expression of Galectin-3 and TGF-β/Smads of the two groups after intervention were compared,the apoptosis rate of cardiomyocytes in each group after intervention was counted,and the pathomorphological changes of myocardial tissue in each group after intervention were observed.Result:After intervention,the levels of dp/dt max,dp/dt min,left ventricular ejection fraction(LVEF)and left ventricular end diastolic pressure(LVEDP)in negative control group and high-dose treatment group were higher than those in medium-dose treatment group,low-dose treatment group and positive control group(P<0.05),and the levels of left ventricular systolic pressure(LVSP)were lower than those in medium-dose treatment group,low-dose treatment group and positive control group(P<0.05).The levels of TNF-α,Hcy and ET in negative control group and high-dose treatment group after intervention were lower than those in middle-dose treatment group,low-dose treatment group and positive control group(P<0.05).After intervention,the protein expression levels of Galectin-3 and TGF-β/Smads in negative control group and high-dose treatment group were lower than those in middle-dose treatment group,low-dose treatment group and positive control group(P<0.05).The apoptosis rates of cardiomyocytes in high-dose treatment group and negative control group were lower than those in middle-dose treatment group,low-dose treatment group and positive control group(P<0.05).Conclusion:For rats with myocardial failure and myocardial fibrosis,treatment with high-dose Salvianolic Acid A can effectively improve cardiac function,inhibit inflammation,reduce the levels of homocysteine and endothelin,reduce cell apoptosis,and then achieve the purpose of inhibiting myocardial fibrosis.