葛根素预防压力过载性心脏肥大的保护作用及机制

Protective effect and mechanism of puerarin prevent cardiac hypertrophy from pressure overload

目的研究葛根素对心脏肥大大鼠的保护作用,并探讨其相关机制。方法将主动脉缩窄术（降主动脉结扎,aortic banding,AB）所致心脏肥大的40只雄性Spraguee Dawley大鼠（体质量80-100g）,分为阳性对照组（control组）、假手术组（shamoperated,SO组）、葛根素组（Pue组）和雷帕霉素组（RAPa组）。检测各组经相应药物治疗后,腺苷酸活化蛋白激酶（5′-adenosine monophosphate kinase,AMPK）的活性及自噬功能。同时,体外检测异丙肾上腺素和3-甲基腺嘌呤所致的心肌影响。结果葛根素组治疗3周后,大鼠明显恢复自噬;葛根素治疗6周后,有效地限制大鼠心脏细胞肥大和细胞凋亡。雷帕霉素组具有相似作用。体外研究,葛根素对异丙肾上腺素所致的H9c2细胞也具有类似的抗肥大和抗细胞凋亡作用。用3-甲基腺嘌呤预处理H9c2细胞,抑制自噬功能后,葛根素的保护作用被阻断。结论葛根素通过AMPK/mTOR信号途径,部分恢复细胞自噬功能,发挥抗心脏细胞肥大和抗细胞凋亡作用。

Objective To certify the protective effects of puerarin on cardiac hypertrophy in rats,and to study the related mechanism.Methods 40 male Spraguee Dawley rats（weight 80-100g）with myocardial hypertrophy caused by aorta surgery（descending aorta ligation,aortic banding,AB）,were divided into the positive control group（con）,sham-operated group（SO）,puerarin group（Pue）and rapamycin group（Rapa）.The activated protein kinase（5′-adenosine monophosphate kinase,AMPK）activity and the function of autophagy were tested.At the same time,the myocardial effects caused by isopropyl adrenaline and 3-methyl adenine were in vitro tested.Results After 3weeks,the rats treated with puerarin recovered autophagy.6weeks after puerarin treatment,the myocyte hypertrophy and apoptosis were effectively limited.Rapamycin group had similar function.In in vitro studies,puerarin also had similar hypertrophy and apoptosis resistance effects in H9c2 cells pretreated by isopropyl.But the protection of puerarin was blocked in H9c2 cells pretreated by 3-methyl adenine.Conclusion All these data indicate that puerarin exerts protective effects against cardiomyocyte hypertrophy and apoptosis,partly by restoration of autophagy through AMPK/mTOR-mediated signaling.