[Activation of JAK2/STAT3 pathway by CPU0213 alleviates myocardial ischemia-reperfusion and oxidative stress injury in rats].

Objective To investigate the role and mechanism of endothelin receptor antagonist CPU0213 in myocardial ischemia-reperfusion (I/R) injury and oxidative stress injury. Methods In order to investigate the role of CPU0213 in I/R, SD rats were randomly divided into sham operation group, ischemia reperfusion injury (I/R) group, CPU0213 treatment group after I/R, CPU0213 and Janus kinase 2 (JAK2) specific inhibitor AG490 treatment group after I/R. In order to investigate the role of CPU0213 in oxidative stress damage, the isolated and characterized cardiomyocytes were cultured and divided into control group, HO oxidative stress group (HO group), oxidative stress damaged group treated with CPU0213, and oxidative stress damaged group treated with CPU0213 and AG490. The rat myocardial I/R models were constructed, and the rats and cardiomyocytes were treated with different treatments according to the experimental requirements. The rat heart was stained with triphenyltetrazolium chloride (TTC) to observe the area of myocardial infarction and the lactate dehydrogenase (LDH) and creatine kinase (CK) activity, flow cytometry to detect the apoptosis rate of cardiomyocytes, CCK-8 method to detect cell growth viability, Western blotting to detect the expression of Bcl2, JAK2, phosphorylated JAK2 (p-JAK2), caspase-3 and caspase-9, STAT3 and phosphorylated STAT3 (p-STAT3). Results After I/R injury in mice, CPU0213 treatment reduced myocardial infarction area, LDH, CK activity and apoptosis rate, but increased the phosphorylation level of JAK2 and STAT3. Compared with I/R combined with CPU0213, I/R combined with CPU0213 and AG490 increased the expression of caspase-3 and caspase-9, decreased significantly the expression of Bcl2 and the cell viability. After oxidative stress damage to cardiomyocytes, CPU0213 treatment reduced LDH, CK activity and cell apoptosis rate, and increased the phosphorylation level of JAK2 and STAT3. In the oxidative stress damaged group treated with CPU0213 and AG490, caspase-3 and caspase-9 expression increased, Bcl2 expression dropped significantly, cell viability decreased significantly. Conclusion The activation of JAK2/STAT3 pathway by CPU0213 can inhibit the apoptosis of cardiomyocytes induced by I/R and oxidative stress.