Role of JNK signalling pathway and platelet-lymphocyte aggregates in myocardial ischemia-reperfusion injury and the cardioprotective effect of ischemic postconditioning in rats

被引:9
作者
Ren, Faxin [1 ]
Mu, Nan [2 ]
Gao, Mingxiao [1 ]
Sun, Jing [1 ]
Zhang, Chuanhuan [1 ]
Sun, Xiaojian [1 ]
Li, Liudong [1 ]
Li, Jun [1 ]
Liu, Tong [3 ]
Tse, Gary [4 ,5 ]
Dong, Mei [1 ]
机构
[1] Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Cardiol, 20 Yuhuangding East Rd, Yantai 264000, Shandong, Peoples R China
[2] Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Gynaecol, Yantai 264000, Shandong, Peoples R China
[3] Tianjin Med Univ, Tianjin Key Lab Ion Mol Funct Cardiovasc Dis, Dept Cardiol, Tianjin Inst Cardiol,Hosp 2, Tianjin 300211, Peoples R China
[4] Chinese Univ Hong Kong, Fac Med, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
[5] Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, 30-32 Ngan Shing St, Hong Kong, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
myocardial ischemia reperfusion injury; ischemia postconditioning; platelet-leukocyte aggregation; c-Jun N-terminal kinase; mitogen-activated protein kinase; INFARCT SIZE; HUMAN HEART; INHIBITION; ACTIVATION; PROTECTS;
D O I
10.3892/mmr.2018.9545
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In myocardial ischemia-reperfusion injury (MIRI), increased activity of the c-Jun N-terminal kinase (JNK) pathway and the activation of platelets that leads to the formation of platelet-leukocyte aggregates (PLAs) have been observed. It was hypothesized that ischemic postconditioning in MIRI exerts cardioprotective effects by altering JNK activity, which in turn leads to reduced PLA levels. A total of 60 rats were randomly divided into 6 groups (n=10 for each group): i) Control; ii) ischemia-reperfusion injury alone; iii) ischemia-reperfusion with postconditioning (PostC group), iv) treatment with the JNK inhibitor-SP600125; v) postC and treatment with anisomycin; and vi) treatment with the JNK activator-anisomycin. Subsequently, the levels of PLA, infarct size, myocardial injury markers (creatinine kinase-muscle/brain and troponin I) and were measured. Western blotting was used to determine the protein expression of phosphorylated-JNK. MIRI led to increased myocardial infarct size that was associated with raised troponin I and creatine kinase-muscle/brain. At different time points of MIRI, the level of PLA gradually increased. Compared with the injury-reperfusion group, the level of PLA in the PostC and Inhibitor-JNK groups was significantly reduced at 60 min and 3 h following reperfusion. MIRI was able to increase the expression of phosphorylated JNK. These effects were significantly reduced by ischemic postC or by treatment with SP600125. By contrast, the addition of anisomycin attenuated these protective effects. JNK is a critical mediator of MIRI. Ischemic postC can reduce the level of PLA during reperfusion by inhibiting the phosphorylation of JNK MAPK, thereby reducing MIRI. Pharmacological inhibition and activation of JNK can improve and reduce cardioprotective effects, respectively. These results explained the mechanism of the cardioprotection of postC and provided novel insight and target for the therapeutic strategy of MIRI.
引用
收藏
页码:5237 / 5242
页数:6
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