Objective:

2

To evaluate the protective effect of Qingxin Jieyu Granule (QXJYG) on myocardial ischemia/reperfusion (I/R) injury by inhibiting cardiomyocyte pyroptosis via circulating exosomes.

Methods:

2

Seventy-five Wistar rats were randomly assigned to 5 groups using a random number table (15 rats per group): sham-operated

model

low-

medium-

and high-dose QXJYG groups (L-QXJYG

M-QXJYG

and H-QXJYG). The L-QXJYG

M-QXJYG

and H-QXJYG groups were administered QXJYG at doses of 2.87

5.73

and 11.46 g/kg

respectively

twice daily via intragastric administration for 28 consecutive days. The model group received an equal volume of normal saline following the same schedule. Following 28 days of administration

myocardial I/R injury was induced 1 h after the final dose. Myocardial infarction size

histopathological changes

and expression of key pyroptosis-related molecules in cardiac tissue were assessed. An oxygen-glucose deprivation/reperfusion model using H9c2 cardiomyocytes was established to investigate the cardioprotective mechanism of QXJYG

emphasizing the role of circulating exosomes in modulating pyroptosis through evaluations of cell viability

pyroptotic morphology

and associated molecular expression.

Results:

2

In vivo

experiments demonstrated that QXJYG significantly reduced myocardial infarction size

improved histopathological morphology

suppressed the inflammatory response

and inhibited myocardial pyroptosis (all

P

<

0.05).

In vitro

QXJYG was shown to enhance H9c2 cardiomyocyte viability

attenuate inflammation

and suppress pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD pathway via circulating exosomes (all

P

<

0.05).

Conclusion:

2

QXJYG alleviates myocardial I/R injury by inhibiting cardiomyocyte pyroptosis through circulating exosomes

potentially via modulation of the NLRP3/ Caspase-1/GSDMD pathway.