OBJECTIVE: To probe into the regulation of trimetazidine on calpain in rats with myocardial ischemia-reperfusion injury and its mechanism of action on cell apoptosis. METHODS: Thirty SD rats were randomly divided into the Sham operation group（Sham group）

model group

and trimetazidine intervention group via the random number table method

with 10 rats in each group. Rats in the Sham group were only sutured but not subjected to coronary artery ligation. Rats in the remaining two groups were all modeled by surgical ligation of the left anterior descending coronary artery（LAD） of the rat myocardium. During the modeling

the Sham group and model group were treated with intragastric administration of 0.9% normal saline

while the trimetazidine intervention group was treated with intragastric administration of 20 mg/kg trimetazidine. Myocardial tissue of rats in each group was observed by Hematoxylin and Eeosin staining

and the levels of myocardial enzymes such as creatine kinase（CK） and lactate dehydrogenase（LDH） were measured by rate method. The apoptotic status of myocardial cells was detected by DNA in situ end labeling（TUNEL） method

and the expression levels of Caspase-3 and B-cell lymphoma 2（Bcl-2） proteins in myocardial tissues were detected by immunohistochemistry. Calpain activity was demonstrated by fluorescence intensity determination with a fluorescence spectrophotometer and expression levels of pyrophosphate-related proteins [nucleotide binding oligomerization domain-like receptor protein 3（NLRP3）

Caspase-1 P10 protein

apoptosis-related macular protein（ASC）

and interleukin-1β（IL-1β）] by Western blotting. RESULTS: In the Sham group

the nuclei of myocardial cells were clear and distinguishable

the myocardial fibers were arranged neatly

and the cytoplasm was stained evenly. In the model group

the nuclei of myocardial cells were condensed

and the myocardial fibers were disorganized; the cells became denatured and became vacuolar

which could be accompanied by inflammatory cell infiltration. In the trimetazidine intervention group

myocardial intercellular substance showed mild edema

and there was no abnormal arrangement of myocardial fibers. No myocardial infarction was observed in the Sham group. The myocardial infarct size of rats in the trimetazidine intervention group was significantly smaller than that of model group（P<0.05）; the levels of myocardial enzyme CK and LDH in the model group and the trimetazidine intervention group were significantly higher than those in Sham group

and the myocardial enzyme indicators in the trimetazidine intervention group were lower than those in the model group（P<0.05）

with statistically significant differences. A small amount of cardiomyocyte apoptosis was observed in Sham group

while the cardiomyocytes in the model group were distributed diffusely

and the number of apoptosis increased significantly. After trimetazidine intervention

myocardial cell apoptosis decreased significantly. The expression level of Caspase-3 protein in the model group was significantly higher than that in the Sham group

and the level of Bal-2 protein decreased significantly（P<0.05）; compared with the model group

the expression level of Caspase-3 protein in the trimetazidine intervention group was lower

and the expression level of Bal-2 protein was higher（P<0.05）

with statistically significant differences. Calpain activity in ischemia/reperfusion（I/R） myocardial cells of rats in the model group was significantly higher than that in the Sham group and trimetazidine intervention group

with statistically significant differences（P<0.05）. There was no significant difference in Calpain activity in I/R myocardial cells of rats between the Sham group and trimetazidine intervention group（P>0.05）. The expression levels of NLRP3

IL-1β

ASC and Caspase-1 P10 protein in the model group and trimetazidine intervention group were significantly higher than those in the Sham group

and the levels of pyroptosis-related proteins in the trimetazidine intervention group were lower than those in the model group

the differences were statistically significant（P<0.05）. CONCLUSIONS: Trimetazidine can reduce cell apoptosis by inhibiting Calpain activity

and then play a role in alleviating the cardiac injury of rats with myocardial ischemia-reperfusion injury.