Protective effect of p38 MAPK inhibitors on myocardial ischemia-reperfusion injury and apoptosis signaling pathway

Objective To explore the protective effect of p38 MAPK inhibitors on myocardial ischemia- reperfusion( I/R) injury and apoptosis signaling pathway. Methods Forty- five male SD rats weighing 250 ~ 300 g were subjected to 30 min occlusion and 120 min reperfusion of the left anterior descending coronary artery( LAD) to induce the I / R injury model. The rats with I / R injury were divided into three groups with 15 for each group: solvent control( vehicle) group,low- dose SB pretreatment( SB- L) group and high- dose SB pretreatment group( SB- H) group. Fifteen age- matched SD rats without ligation were selected as sham group. The SB- L group and SB- H group were injected 50,100 μg SB 30min before LAD ligation. The other two groups were injected with same volume of saline. The levels of plasma tumor necrosis factor( TNF-α) were measured preoperative( T0),30 min after ischemia( T1),60 min( T2),120 min( T3) and 180 min after( T4) reperfusion. The cardiac function after I / R( end- diastolic pressure LVEDP,left ventricular systolic mean pressure LVSP,FS fractional shortening and ejection fraction EF) were investigated. The rats were sacrificed and TTC staining was used to detect the degree and extent of ischemic and infarction. The heart tissue was embedded and the morphological changes were observed by HE staining. The protein levels of p38 and its phosphorylated form of p- p38 were investigated. Results Compared with sham group,there were higher levels of TNF- α,lower levels of LVSP,FS and EF,and elevated LVEDP,myocardial ratio of p- p38 / p38,extent of ischemia and infarction in vehicle group with significant difference. There were dissolved and necrotic muscle fibers,increased myocardial interstitial gap and edema in Vehicle group. SB can mitigate the above anomalies and cardiac pathology with statistically significance with sham group and vehicle group( P 0. 05). There was an enhancing effect in SB- H group versus SB- L group with significant differences( P 0. 05). Conclusion SB can mitigate the I / R injury with the effect of decreasing extent of ischemia and infarction and improvement on cardiac function and inflammation.