Author + information
To investigate the effects and mitochondrial dynamics mechanisms of penehyclidine hydrochloride (PHC) on ischemia/reperfusion (I/R)-induced myocardial injury.
A rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30 min followed by 3 h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected. Evans blue/TTC double staining was performed to assess infarct size. Cardiomyocyte apoptosis was evaluated by TUNEL assay. The oxygen stress markers was detected by ELISA. Western blot and real time fluorescent quantitative PCR was performed to analyze the expression of Drp1, Mfn1, Mfn2. Meanwhile, the rats were given a single injection of PHC before I/R. The effects of PHC on myocardial infarct and cardiac function were investigated after 7 days post-reperfusion.
Our results showed that PHC pretreatment improved imbalance of mitochondrial dynamics induced by oxidative stressor in IRI. PHC preconditioning alleviated apoptotic rate of cardiomyocytes by improving imbalance of mitochondrial dynamics in IRI. Meanwhile, we showed that PHC remarkably improved cardiac function, myocardial injury by decreasing infarct size and attenuated levels of myocardial enzyme. Additionally, PHC also exerted long-term cardioprotection in a rat model of I/R injury by decreasing infarct size and improving cardiac function.
These results suggest that PHC can efficiently protect the rats against I/R-induced myocardial injury via mechanism of mitochondrial dynamics.