@article{APS7412,
author = {Man-man Zhao and Jin-yan Yang and Xin-bao Wang and Chao-shu Tang and Jun-bao Du and Hong-fang Jin},
title = {The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats},
journal = {Acta Pharmacologica Sinica},
volume = {34},
number = {4},
year = {2016},
keywords = {},
abstract = {Man-man ZHAO1, Jin-yan YANG1, Xin-bao WANG1, Chao-shu TANG2, 3, Jun-bao DU1, 2, Hong-fang JIN1, *
1Department of Pediatrics, Peking University First Hospital, Beijing 100034, China; 2Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China; 3Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100191, China
Aim: To explore the mechanisms underlying the protection by SO2 preconditioning against rat myocardial ischemia/reperfusion (I/R) injury.
Methods: Male Wistar rats underwent 30-min left coronary artery ligation followed by 120-min reperfusion. An SO2 donor (1 μmol/kg) was intravenously injected 10 min before the ischemia, while LY294002 (0.3 mg/kg) was intravenously injected 30 min before the ischemia. Plasma activities of LDH and CK were measured with an automatic enzyme analyzer. Myocardial infarct size was detected using Evans-TTC method. The activities of caspase-3 and -9 in myocardium were assayed using a commercial kit, and the levels of p-Akt, Akt, PI3K and p-PI3K were examined with Western blotting.
Results: Pretreatment with SO2 significantly reduced the myocardial infarct size and plasma LDH and CK activities, as well as myocardial caspase-3 and -9 activities in the rats. Furthermore, the pretreatment significantly increased the expression levels of myocardial p-Akt and p-PI3K p85. Administration of the PI3K inhibitor LY294002 blocked all the effects induced by SO2 pretreatment.
Conclusion: The results suggest that the PI3K/Akt pathway mediates the protective effects of SO2 preconditioning against myocardial I/R injury in rats.
Keywords: sulfur dioxide; ischemia/reperfusion; heart infarct; preconditioning; LDH; creatine kinase; caspase-3; caspase-9; PI3K/Akt pathway; LY294002
This work was supported by the Major Basic Research Program of China (2012CB517806 and 2011CB503904) and the National Natural Science Foundation of China (81121061, 81070111, 31130030, and 81070212).
* To whom correspondence should be addressed.
E-mail jinhongfang51@126.com
Received 2012-10-11 Accepted 2012-12-30},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7412}
}