Conclusion
CRY may alleviate MIRI by inhibiting ERS-dependent apoptosis by activating the JAK1/STAT3 signaling pathway.
Methods
A rat model of myocardial ischemia and reperfusion injury (MIRI) was created and subjected to cryptotanshinone (CRY) with or without JAK1 inhibitor filgotinib (FILGO) treatment. H&E staining was used for histopathologic evaluation of heart injury, and TTC staining was employed for evaluation of the infarct size. Western blotting and immunofluorescence were used to measure the protein expression and qRT-PCR for determining mRNA expression.
Objective
Myocardial ischemia is the stoppage or insufficiency of blood flow to the myocardium, depriving cells of oxygen supply which leads to their apoptosis or death. Currently, the management of patients has improved, making it possible to reduce myocardial infarction injury with new strategies of reperfusion and pharmacologic treatment.
Results
CRY significantly reduced the area of the infarct, the number of apoptotic cells, and the concentrations of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) induced by ischemia/reperfusion (I/R). Subsequent analysis showed that CRY repressed the expression of caspase-12, CHOP, and GRP78, but enhanced the phosphorylation of JAK and STAT3. However, FILGO treatment markedly abolished the beneficial effect of CRY pretreatment on cardiomyocyte damage, apoptosis, cardiac function, and inhibition of endoplasmic reticulum stress (ERS)-dependent apoptosis marker proteins.