1. DIDS Reduces Ischemia/Reperfusion-Induced Myocardial Injury in Rats
- Author
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Xiaoming Wang, Yanan Cao, Mingzhi Shen, Bo Wang, Weiwei Zhang, Yan Liu, Xiaole He, Lin Wang, Yuesheng Xia, Mingge Ding, Xihui Xu, and Jun Ren
- Subjects
Apoptosis ,DIDS ,Ischemia/Reperfusion injury ,Cardiac function ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: Anion channels such as chloride channel are known to participate in the regulation of a wide variety of cellular processes including development, differentiation, proliferation, apoptosis and regeneration. This study was designed to examine the effect of the non-selective anion channel blocker 4,4'-Diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS) on cardiac function and apoptosis using a rat model of ischemia/reperfusion (I/R). Methods: Fifty male SD rats were randomly divided into the following groups including sham, I/R and I/R+DIDS (7, 14 or 28 mg/kg). In DIDS group, rats received DIDS treatment (4 ml/kg/hr) at the beginning of reperfusion for 2 hrs using a programmed micro-pump. Cardiac function was evaluated including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) as well as positive and negative maximal derivatives of left ventricular pressure (± dP/dtmax). Myocardial infarct size was detected using the double staining with 2, 3, 5-triphenyl-2H-tetra-zolium chloride (TTC) and Evan's blue dye. DNA ladder, TUNEL assay, Bax and Bcl-2 protein levels were evaluated. Levels of ROS and Akt phosphorylation were detected. Results: I/R injury compromised cardiac function as manifested by reduced LVSP and ± dP/dtmax as well as pronounced apoptosis. I/R-induced cardiac anomalies were markedly ameliorated by DIDS. DIDS retarded I/R-induced myocardial infarct and apoptosis. In addition, DIDS ameliorated I/R-induced ROS production and Akt dephosphorylation in the heart. Conclusion: Taken together, our data revealed that DIDS may protect cardiomyocytes against I/R injury as evidenced by improved cardiac function, Bcl-2, Akt phosphorylation, and reduced myocardial apoptosis, Bax expression, ROS production and myocardial infarct size.
- Published
- 2015
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