Danqi Tablet Regulates Energy Metabolism in Ischemic Heart Rat Model through AMPK/SIRT1-PGC-1α Pathway

Objective To investigate the cardioprotective effect of Danqi Tablet (DQT) on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha). Methods Rat ischemic heart model was induced by ligation of left anterior descending coronary artery. Totally 40 Sprague-Dawley rats were randomly divided into sham group, model group, DQT group (1.5 mg/kg daily) and trimetazidine (TMZ) group (6.3 mg/kg daily) according to a random number table, 10 rats in each group. Twenty-eight days after continuous administration, cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining. The level of adenosine triphosphate (ATP) in myocardial cells was measured by ATP assay kit. Expressions level of key transcriptional regulators, including PGC-1 alpha, Sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and downstream targets of PGC-1 alpha, such as mitofusin 1 (MFN1), mitofusin 2 (MFN2) and superoxide dismutase 2 (SOD2) were measured by Western blot. Expression level of PGC-1 alpha was examined by immunohistochemical staining. Results The rat ischemic heart model was successfully induced and the heart function in model group was compromised. Compared with the model group, DQT exerted cardioprotective effects, up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues (P<0.01). The expressions of PGC-1 alpha, SIRT1 and AMPK were increased in the DQT group (all P<0.05). Furthermore, the downstream targets, including MFN1, MFN2 and SOD2 were up-regulated (PP<0.01). Compared with the TMZ group, the expression levels of PGC-1 alpha, MFN1 and SOD2 were increased by DQT treatment (PP<0.01). Conclusion DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1 -PGC-1 alpha pathway. PGC-1 alpha might serve as a promising target in the treatment of ischemic heart disease.

Automated summary

Danqi Tablet (DQT) has a cardioprotective effect on ischemic heart model rats, increasing ATP production in myocardial cells and inhibiting inflammation. It regulates energy metabolism through the AMPK/SIRT1-PGC-1 alpha pathway, suggesting a potential target for treating ischemic heart disease.