Shenqi Lixin Decoction improves cardiac function in rats with adriamycin-induced heart failure through modulation of PGC-1α and mitochondrial apoptosis pathway

Background: Heart failure (HF) is a complex clinical syndrome and a serious manifestation or late stage of various heart diseases. This study aimed to explore the protective effects and underlying mechanisms of Shenqi Lixin Decoction (SQLXD) in HF.

Methods: A HF rat model was induced by intraperitoneal injection of adriamycin (3 mg/kg in the first 3 weeks, 2 mg/kg in the next 3 weeks, once a week, subcutaneous injection, 6 weeks cumulative dose is 15 mg/kg). After 4 weeks of intragastric administration of SQLXD (9.975, 19.95, 39.90 g/kg, once a day, gavage), the indexes of cardiac function were measured by cardiac color Doppler ultrasound, the cardiac muscle structure and pathological changes were observed by transmission electron microscope, hematoxylin-eosin (HE) staining and Masson. The plasma N-terminal B-type natriuretic peptide (NT-proBNP) level and myocardial tissue adenosine triphosphate (ATP) content were detected by ELISA. FITC detected the cardiomyocyte apoptosis rate (CMAR) labeled Annexin V/PI. Expression of B cell lymphoma factor 2 (Bcl-2), Bcl-2 associated X (Bax), cysteine protease-3 (Caspase-3), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA in myocardial tissue were detected by real-time PCR (RT-PCR). The expression of Bcl-2, Bax, Caspase-3 and P53 protein in myocardial tissue were detected by Western blot.

Results: Compared to the normal group, left ventricular end systolic diameter (LVSD), left ventricular end diastolic diameter (LVDD), CMAR and the expression of P53 protein, mRNA and protein of Bax and Caspase-3 were significantly increased in model group, while left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), stroke volume (SV) and the expression of Bcl-2 protein, mRNA of PGC-1α and Bcl-2 were significantly reduced. Compared to the model group, LVSD, LVDD, CMAR and the expressions of P53 protein, mRNA and protein of Bax and Caspase-3 in the medium and high dose SQLXD groups and the control group were significantly decreased, while LVEF, LVFS, SV and the expression of Bcl-2 protein, mRNA of PGC-1α and Bcl-2 were obviously increased. Pathological findings by transmission electron microscope, Masson, and HE staining all revealed protective effects of SQLXD on heart.

Conclusions: SQLXD can effectively protect HF rats' hearts. The potential mechanism may be related to the modulation of the expression of PGC-1α and the mitochondrial apoptosis pathway.