Conclusion
PA protects against MI/R, possibly by modulating ER stress, apoptosis and the Notch1/Hes1 signalling pathways. These findings indicate that PA may be a promising candidate for treating ischaemic heart diseases.
Methods
C57BL/6 male mice were randomly divided into sham, MI/R, MI/R + PA-10, MI/R + PA-20 and MI/R + PA-40 groups. In vivo MI/R model was established by ligating the anterior descending coronary artery of the heart. In vitro stimulated IR cell model was constructed by using the rat cardiomyocyte H9C2 cell line. Mice in the treatment groups were intraperitoneally injected with PA (10, 20, 40 mg/kg) for 30 days then subjected to surgery, and cells in the experimental group were pre-treated with PA (1, 10 or 100 μmol/L). After treatment, mouse heart function, myocardial injury markers, myocardial infarction and Notch1/Hes1 expression, endoplasmic reticulum stress markers, and apoptosis-related proteins were determined.
Objective
To examine the therapeutic effect of PA on myocardial ischaemia-reperfusion (I/R) injury. Materials and
Results
In vivo, PA treatment improved hemodynamic parameter changes and myocardial enzymes, increased the left ventricular ejection fraction and left ventricular fractional shortening, reduced the left ventricular end-systolic diameter and inhibited CK-MB, cTnI and cTnT levels. In addition, PA attenuated myocardial tissue damage and apoptosis. PA treatment elevated Notch1, NICD and Hes1 levels and suppressed the levels of ATF4, p-PERK/PERK, and cleaved caspase-3/caspase-3 in vitro and in vivo.