Objective:

2

To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern

substrate utilization

and mechanistic modulation.

Methods:

2

In vivo

echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation.

In vitro

a hypoxia-induced H9C2 model was established

mitochondrial damage was evaluated by flow cytometry

and nuclear translocation of hypoxia-inducible factor-1α (HIF-1α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions.

Results:

2

QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1α pathway

and improved cardiac function in HF rats. Specifically

QSG promoted HIF-1α expression and entry into the nucleus at high levels of hypoxia (

P

<

0.05)

thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1α at relatively low le

vels of hypoxia (

P

<

0.05)

promoting the increased lipid metabolism.

Conclusions:

2

QSG regulates the protein stability of HIF-1α

thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.