黄芪甲苷通过AMPK/ACSS2/PPARα信号通路改善心肌细胞能量代谢的机制研究

Mechanism study of Astragaloside Ⅳ improving energy metabolism of myocardial cells through AMPK/ACSS2/PPARα signaling pathway

目的:探讨黄芪甲苷对血管紧张素Ⅱ(AngⅡ)诱导的HL-1心肌细胞肥大的作用机制。方法:将HL-1心肌细胞分为空白组,AngⅡ组,黄芪甲苷低、中、高剂量组,共同培养24 h。收集各组细胞,CCK8检测细胞活性,检测细胞ATP含量,免疫荧光检测细胞ACSS2的表达情况,RT-PCR、Western Blot检测细胞心肌肥大相关指标mRNA及蛋白表达情况。结果:与AngⅡ组比较,黄芪甲苷各剂量组细胞活力显著增加(P<0.01),细胞内ATP含量显著升高(P<0.01),ANP、BNP、Myh7 mRNA及蛋白表达水平降低(P<0.01),AMPK、ACSS2、PPARαmRNA水平显著升高(P<0.01),p-AMPK/AMPK、ACSS2、PPARα、PGC-1α蛋白表达显著增加(P<0.01)。结论:黄芪甲苷可以抑制AngⅡ诱导的心肌细胞肥大,改善心肌细胞能量代谢,其机制可能与激活AMPK/ACSS2/PPARα信号通路有关。

Objective:The study mainly discussed the effect of Astragaloside Ⅳ(AS-Ⅳ) on HL-1 cardiomyocytes induced by angiotensin Ⅱ(AngⅡ) and explored the possible mechanisms.Methods:The experiment was divided into control group,AngⅡgroup,astragaloside Ⅳ low,medium,and high dose groups.The cell viability and intracellular ATP concentration were tested in each group after being cultured for 24 hours.The expression of ACSS2 in each group was detected by Immunofluorescence.The expression of myocardial hypertrophy markers were detected by RT-PCR and Western Blot.Results:Compared with the AngⅡgroup,the cell viability and ATP contents were significantly increased(P<0.01).The expression of AMPK,ACSS2,PPARα mRNA were increased and the protein expression levels of p-AMPK/AMPK,ACSS2,PPARα,and PGC-1α were increased significantly in AS-Ⅳ groups while the mRNA and protein levels of ANP,BNP,Myh7 were significantly reduced(P<0.01).Conclusion:AS-Ⅳ can inhibit cardiomyocyte hypertrophy induced by AngⅡ,and improve energy metabolism on HL-1 cell,and its mechanism may be associated with the activation of AMPK/ACSS2/PPARα signaling pathway.