YQFM alleviated cardiac hypertrophy by apoptosis inhibition and autophagy regulation via PI3K/AKT/mTOR pathway

Abstract

Ethnopharmacological relevanceAs a traditional compound preparation of Chinese medicine, Yiqi Fumai lyophilized injection (YQFM) has protective effects on various cardiac diseases including cardiac hypertrophy, which is the primary cause of arrhythmia. However, the involved mechanism remains unclear. Aim of the study: This study was projected to investigate whether YQFM could prevent cardiac hypertrophy and arrhythmia concurrence. Materials and Methods: The cardiac hypertrophy rats were established by transverse aortic ligation and the H9c2 hypertrophy cardiomyocyte was induced by angiotensin II (AngII). The electrocardiogram (ECG) was conducted to estimate the arrhythmia occurrence of cardiac hypertrophy rats under isoprenaline (iso) treatment. The cardiac related indicators and histopathology were also detected. The protective effects of YQFM on H9c2 hypertrophy cardiomyocyte were determined by the cell size measurement, apoptosis detection and mitochondrial membrane potential measurement. The cardiac hypertrophy relative proteins (ANP and BNP), autophagy related factors (LC3II, p62 and Beclin-1), apoptosis related markers (p53, caspase 3, Bax and Bcl-2) and the PI3K/AKT/mTOR pathway expressions were all measured by Western blot. Results: YQFM decreased the arrhythmia occurrence and improved cardiac function in cardiac hypertrophy rats. YQFM also reduced the H9c2 cardiomyocyte size and alleviated the cardiomyocyte apoptosis induced by AngII. In addition, YQFM inhibited cell apoptosis by increasing Bcl-2/Bax ratio and decreasing caspase 3 and p53 expressions in vitro and vivo. Meanwhile, YQFM regulated the autophagy pathway by down-regulating of LC3II and Beclin-1 expressions, as well as up-regulating of p62 expression. Finally, the results showed that YQFM could activate the PI3K/AKT/mTOR pathway by enhancing the p-AKT, p-PI3K and p-mTOR expressions. Conclusion: Our results displayed that YQFM attenuated the cardiac hypertrophy by apoptosis inhibition and autophagy regulation via PI3K/AKT/mTOR pathway.