Gradual increased reperfusion plays better cardioprotective role through MAPK pathway / 中华急诊医学杂志

ABSTRACT

Objective To aims Study cardioprotection of different postconditioning algorithm,and investigate the role of MAPK pathway in the process.Methods Sixty SD rats were randomly (random number) divided into 5 groups,sham operation group,reperfusion/injury group (I/R group),gradual decreased reperfusion in postconditioning (GDR,30/10-25/15-15/25-10/30s of reperfusion/re occlusion) group,routine reperfusion in postconditioning (ER,4 cycles of 20/20s of reperfusion/reocclusion) group,and gradual increased reperfusion in postconditioning (GIR,10/30-15/25-25/15-30/10s of reperfusion/re-occlusion) group.Acute myocardial infarction and ischemic postconditioning models were established in the rats.Six hours after reperfusion,3 rats of each group were sacrificed and myocardial tissue were taken out to measure the level of phosphorylation of extracellular signal regulated protein kinase (P-ERK),Phosphorylation of stress-activated protein kinase (stress activated protein kinase,P-JNK),phosphorylation of p38 MAPK (P-p38),tumor necrosis factor-α (TNF-o),cysteine and aspartic protease-8 (Caspase-8) in myocardial tissue and the expression of cytochrome C in the cytosol using Western Blot method.Twenty-four hours after reperfusion all the remaining rats were to measure hemodynamic variables and level of myocardial enzyme,and myocardial tissue were taken out to determine myocardial apoptosis.A one-way analysis of variance (ANOVA) was used,and q tests were employed to determine differences in individual variables existed between groups.Results All three postconditioning modalities were found to provide cardioprotection (P ＜ 0.05) compared with I/R without preconditioning.The GIR provided the best cardioprotection effect,followed by ER and then GDR.Apoptotic index and serum marker levels were reduced far more in GIR than those in ER (P ＜ 0.05).The enhanced cardioprotection provided by GIR was accompanied by significantly increased levels of P-ERK1/2 [(1.82 ± 0.22) vs.(1.54±0.32),P＜0.05],and lower levels of P-p38 [(0.82±0.26) vs.(1.63 ± 0.24)],P-JNK [(0.76±0.28) vs.(1.33±0.21),TNF-o [(0.62±0.20) vs.(1.00±0.12)],Caspase-8 [(0.61 ±0.21) vs.(1.00±0.30)],Cyt-c [(0.66±0.16) vs.(1.68±0.22)] in the cytoplasm (P ＜ 0.05,all compared with ER).In addition,all the variables measured here were significantly improved in the GIR group relative to the GDR group (P ＜ 0.05).Conclusions The method of gradual increased reperfusion in postconditioning could attenuate reperfusion injury more significantly than routine algorithm whereby MAPK pathway played an important role in the process.