Protective effect of Ebselen on myocardial ischemia reperfusion injury through regulating MAPK pathway

Objective To research the correlation between the protective effect of Ebselen on myocardial ischemia reperfusion injury and MAPK pathway. Methods Thirty-six male Wistar rats were randomly divided into sham operation group(Sham), Ischemia reperfusion group (IR-Control), Ebselen + ischemia reperfusion group (Ebselen+IR) and Ebselen group (Ebselen). The myocardial ischemia reperfusion rat model was established. The myocardial apoptosis and necrosis were evaluated by injury score and observed by HE staining; The expression of serum TNF-α, IL-6, and tissue TGFβ1 were detected by ELISA, and the expression of MAPK pathway related proteins were detected by Western blotting. Results Compared with ischemia reperfusion group, Ebselen pretreatment significantly decreased myocardial necrosis, inflammation and edema, histological injury score, Ebselen pretreatment significantly reduced TNF-α induced by ischemia reperfusion (P<0.05) and also IL-6, TGFβ1 (P<0.01). Besides, ischemia reperfusion + Ebselen group reduced the level of ERK1/2 and reduced the expression of phosphorylation of JNK and p38 induced by ischemia reperfusion injury, p-JNK increased by 0.34±0.06, p-p38 increased by 0.42±0.10, p-ERK1/2 decreased by 0.35±0.07, P<0.001. Ebselen + ischemia reperfusion group increased the level of ERK1/2 and reduce the phosphorylation of JNK and p38 caused by ischemia reperfusion injury, p-JNK decreased by 0.17±0.05 (P<0.001), p-p38 decreased by 0.16±0.03 (P<0.01), p-ERK1/2 increased 0.09±0.02 (P<0.05). Conclusion Ebselen treatment played a protective effect on myocardial ischemia reperfusion injury and its mechanism may be related to the MAPK pathway.