黄芪甲苷通过p65通路调节心肌能量代谢延缓心肌肥厚发展的机制研究

心肌肥厚在发展过程中炎症因子水平增加，同时心脏的代谢底物由脂肪酸为主转为以葡萄糖氧化为主，并伴随着糖和脂代谢酶的改变。过氧化物酶体增殖物激活受体γ辅激活因子1（PGC-1α）是调节脂代谢转录的辅激活因子。炎症背景下核转录因子κB （NF-κB）p65通过下调PGC-1α通路加重心肌损害，因此我们推测p65对PGC-1α的调节作用也参与了心肌肥厚的发生发展，而具有心血管保护作用的黄芪甲苷对可通过PGC-1α与p65通路防治心肌肥厚的发展。为此我们将采用现代分子生物手段，结合基因转染和基因敲除小鼠，观察PGC-1α与p65通路在心肌肥厚发展过程中的作用以及黄芪甲苷对该通路的调节，进一步阐明心肌肥厚发生发展机制，并为黄芪甲苷的合理开发提供科学的依据。

Cardiac hypertrophy is accompanied with increased pro-inflammatory cytokines, shift in cardiac energy substrate utilization towards glucose and lactic acid from fatty acids, and changes in energy metabolism enzyme. The PPARγ coacivator-1α(PGC-1α) serve as inducible boosters of downstream transcription fators that control the expression of genes involved in glucose and fatty acide metabolism. Previous studies indicated that nucleus factor-κB(NF-κB)p65 downregulate PGC-1αand aggravate heart failure under inflammation backgroud. So we speculate that regulation effect of p65 on PGC-1α participate in the process of cardiac hypertrophy. Astragaloside IV, which has protective effect on cardivscular disease,could attanuated myocardial hypertrophy via PGC-1αand p65 signaling pathway. Therefore,we will use modern molecular biology technology and combination with transfection and siRNA to investigate the role of PGC-1α and p65 in cardiac hypertrophy, and observe the effect of astragaloside, on PGC-1α and p65 in cardiac hypertrophy. Our study will futher clarity the mechanism of cardiac hypertrophy and provide scientific evidence for the use of astragaloside IV.