Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P < 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P < 0.05). The serum IL-2, IFN-[beta], and TNF-[alpha] in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P < 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P < 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P < 0.01), while the level of p62 protein was significantly increased (P < 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P < 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway. Keywords: Autophagy, Combination, Heart Failure, Huangqi granule, Resuvastatin, Therapeutic effect Abbreviations Used: 5'AMP-activated protein kinase, AMPK; S-methylglutathione, GSM; Heart failure, HF; Huangqi granule, HQ; Interferon-p, IFN-p; lnterleukin-2, IL-2; Microtubule-associated proteins 1A/1B light chain 3B, LC3; Left ventricular end-diastolic dimension, LVEDD; Left ventricular ejection fraction, LVEF; Left ventricular end-systolic dimension, LVESD; Left ventricular posterior wall thickness at end-diastole, LVPWTd; Left ventricular posterior wall thickness at end-systole, LVPWTs; Mammalian target of ra