葛根素预处理对心肌梗死模型大鼠HMGB1的表达及心肌细胞凋亡的影响

Effects of puerarin pretreatment on HMGB1 expression and cardiomyocyte apoptosis in rats with myocardial infarction

目的:探讨葛根素预处理对大鼠心肌梗死(MI)模型中高迁移率族蛋白B1(HMGB1)的表达、心肌细胞凋亡和心功能的影响。方法:将30只SD大鼠随机分为假手术组、MI组、MI+葛根素组,每组10只。通过结扎冠状动脉左前降支建立大鼠MI模型,MI+葛根素组在MI造模前通过腹腔注射给予葛根素120 mg/kg·d^-1,连续7 d,1次/d。分别应用超声心动图、TUNEL染色及Western blotting检测各组大鼠心功能、心肌细胞凋亡率及HMGB1、cleaved caspase-3、Bcl-2和Bax的蛋白表达水平。结果:与假手术组比较,MI组大鼠左心室射血分数(LVEF)及左心室短轴缩短率(LVFS)明显降低(P<0.05),而左心室舒张末期内径(LVEDd)及左心室收缩末期内径(LVESd)明显增加(P<0.05);心肌细胞凋亡率显著增加(P<0.05);心肌组织HMGB1、cleaved caspase-3及Bax蛋白表达显著升高(P<0.05),而Bcl-2蛋白表达显著下降(P<0.05)。与MI组比较,MI+葛根素组大鼠LVEF及LVFS明显升高(P<0.05),而LVEDd及LVESd明显减少(P<0.05);心肌细胞凋亡率显著降低(P<0.05);心肌组织HMGB1、cleaved caspase-3及Bax蛋白表达显著下降(P<0.05),Bcl-2蛋白表达显著增加(P<0.05)。结论:葛根素预处理可明显抑制MI后心肌细胞凋亡,从而改善心功能不全和心肌损伤,其机制可能是通过抑制HMGB1和下调cleaved caspase-3及Bax表达,上调Bcl-2蛋白表达来实现。

Objective:To explore the effects of puerarin pretreatment on the expression of high mobility group protein box B1(HMGB1),cardiomyocyte apoptosis and cardiac function in rat myocardial infarction(MI)model.Methods:Thirty SD rats were randomly divided into sham operation group,MI group and MI+puerarin group,with 10 rats in each group.The rat model of MI was established by ligating the left anterior descending branch of coronary artery.MI+puerarin group was injected with puerarin 120 mg/kg d^-1 intraperitoneally before the establishment of MI model,once a day for 7 days.Echocardiography,TUNEL staining and Western blot were used to detect cardiac function,cardiomyocyte apoptosis rate and protein expression of HMGB1,cleaved caspase-3,Bcl-2 and Bax.Results:Compared with the sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were significantly decreased(P<0.05),while the left ventricular enddiastolic diameter(LVEDd)and left ventricular end-systolic diameter(LVESd)in MI group were significantly increased(P<0.05).The apoptosis rate of cardiomyocytes was significantly increased in the MI group(P<0.05).The expression of HMGB1,cleaved caspase-3 and Bax protein in myocardium increased significantly(P<0.05),while the expression of Bcl-2 protein decreased significantly(P<0.05).Compared with MI group,LVEF and LVFS in MI+puerarin group increased significantly(P<0.05),while LVEDd and LVESd decreased significantly(P<0.05),the apoptosis rate of cardiomyocytes decreased significantly(P<0.05),the expression of HMGB1,cleaved caspase-3 and Bax protein decreased significantly(P<0.05),and the expression of Bcl-2 protein increased significantly(P<0.05).Conclusion:Puerarin pretreatment can significantly inhibit cardiomyocyte apoptosis after MI,thus improving cardiac dysfunction and myocardial injury.The mechanism may be related toinhibiting HMGB1,down-regulating cleaved caspase-3 and Bax expression,and up-regulating Bcl-2 protein expression.