Nobiletin Post-conditioning Attenuates Myocardial Cell Apoptosis Following Myocardial Ischemia-reperfusion Injury

Objective Research shows that the myocardial ischemia reperfusion injury(MIRI),which is induced by the treatment for myocardial infarction revascularization seriously affect the prognosis of patients. Therefore,to reduce MIRI has become a focus in the study of cardiology. Nobiletin, a citrus polymethoxylated flavone, is reported to possess various effective pharmacological activities.In this study,we try to determine the effect of post-conditioning with nobiletin on myocardial ischemia-reperfusion injury,and its relationship with PI3K/Akt signal pathway.Methods Forty-eight healthy male C57BL/6 rats were randomly allocated into sham operation group(Sham group), ischemia/reperfusion injury group(I/R group),nobiletin post-conditioning group(NOB group) and nobiletin post-conditioning +LY294002 group(NL group).Myocardial I/R injury was established by occlusion of anterior descending branch of left coronary artery for 30 min followed by120 min reperfusion. The infarct size and the area at risk were measured by double-staining of Evans Blue and TTC. Myocardial apoptosis was detected by T UNEL. The concertration of MDA was measured by thiobarbituric acid and xant hine oxidase was used to measure SOD.Western blot was adopted to detect the expression of the Akt、Bcl-2、Bax、Caspase-3 and ratio of Bcl-2/Bax.Results Compared with the sham group, the infarct size and apoptosis of I/R group was significantly increased, the expression of Bax and caspase-3 was up-regulated,Akt and Bcl-2 was decreased,and the ratio of Bcl-2/Bax was decreased,the concertration of MDA was significantly increased,but SOD was significantly decreased(P <0.001).Compared with the I/R group,the infarct size and apoptosis of NOB group was significantly decreased, the expression of Akt and Bcl-2 was up-regulated,while the expression of Bax and caspase-3 was down-regulated,and the ratio of Bcl-2/Bax was increased, the concertration of MDA was significantly decreased,but SOD was significantly increased(P<0.001).Compared with the NOB group,the infarct size and apoptosis of NL group was significantly increased, the expression of Akt and Bcl-2was down-regulated,while the expression of Bax and caspase-3 was up-regulated,and the ratio of Bcl-2/Bax was decreased, the concertration of MDA was significantly increased,but SOD was significantly decreased(P<0.001).Conclusion Nobiletin post-conditioning attenuates myocardial ischemia-reperfusion injury and apoptosis,the mechanism associated with PI3K-Akt pathway activation reduces oxidative stress.