Aim To investigate the effects and Mechanisms of chloride channel inhibitor, 4, 4′- Diisothiocyanostilbene-2, 2′- disulfonic acid (DIDS) and free radical scavenger, Edaravone (EDRV) on myocardial ischaemia/reperfusion injury (I/RI)in vivo.
Methods Male Sprague-Dawley rats, subjected to 30 min of myocardial ischaemia and 4 h of reperfusion, were divided into five groups: sham group, I/RI group, DIDS group, EDRV group and DIDS+EDRV group. Left ventricular systolic pressure (LVSP), The maximal first derivative of developed pressure (±dp/dtmax), Myocardial infarction size, serum creatine kinase (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) concentration, myocardial apoptotic index, reactive oxygen species (ROS) were detected.
Results There were no statistical difference in heart rate in each animal suffering myocardial ischaemia/reperfusion compared with sham group (p>0.05, n=8). LVSP and ±dp/dtmax were decreased during the period of myocardial ischaemia except sham but there was no statistical difference (p>0.05, n=8), However, following reperfusion, the data showed that DIDS and EDRV significantly improved myocardial function in I/RI rats (n=8, p<0.05) and DIDS+EDRV combined administration had a much stronger cardioprotective effect than DIDS or EDRV did alone (n=8, p<0.05); the levels of activity of serum creatine kinase (CK) (n=8), lactate dehydrogenase (LDH) (n=8), myocardial infarction size (n=8), myocardial apoptotic index (n=6)showed that there were no statistical difference was observed between DIDS and EDRV groups, DIDS+EDRV treatment further decreased compared with DIDS or EDRV treatment alone (p<0.05) for the above-mentioned results; and the levels of the concentration of malondialdehyd (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), O2− and OH·showed that DIDS reduces free radical weaker than EDRV (p<0.05, n=8), and DIDS+EDRV combined administration had a stronger cardioprotective effect than DIDS or EDRV did alone and combined administration possesses synergies action (p<0.05, n=8).
Conclusion 1. DIDS and EDRV protect myocardium from MI/R injury via improving cardiac function, reducing infarct size and suppressing cardiomyocyte apoptosis; 2. The mechanisms of cardioprotective effects of DIDS and EDRV were involved in inhibition of ROS activity. The protective effect of combined administration can be further enhanced, suggesting DIDS protects ischaemia/reperfusion injury myocardium via other distinctive mechanisms except above.
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Funding The research was supported by the National Natural Science Foundation of China (NSFC, Nos. 30770847).