Role of JNK and p38MAPK signaling pathways in attenuation of myocardial ischemia-reperfusion injury by morphine postconditioning：an in vitro experiment
10.3760∕cma.j.issn.0254-1416.2016.11.018
- VernacularTitle:JNK和p38 MAP K信号通路在吗啡后处理减轻大鼠心肌再灌注损伤中的作用：离体实验
- Author:
Henghua SHEN
;
Zuolei CHEN
;
Rundong TANG
;
Yingzhi LIU
;
Haichen CHU
- Keywords:
JNK mitogen-activated protein kinases;
p38 mitogen-activated protein kinases;
Signal transduction;
Morphine;
Ischemic postconditioning;
Reperfusion injury
- From:
Chinese Journal of Anesthesiology
2016;36(11):1349-1352
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of c?Jun N?terminal kinase ( JNK) and p38 mitogen?ac?tivated protein kinase ( p38MAPK) signaling pathways in attenuation of myocardial ischemia?reperfusion ( I∕R) injury by morphine postconditioning. Methods Healthy adult male Sprague?Dawley rats, weighing 180-240 g, were used in the study. Their hearts were excised and retrogradely perfused in a Langendorff apparatus with Krebs?Ringer ( K?R) buffer saturated with 95% O2?5% O2 at 37℃. After 15 min of equili?bration, 52 isolated hearts were divided into 4 groups ( n=13 each) using a random number table: control group (group C), I∕R group, morphine postconditioning group (group MP), and morphine postcondition?ing plus anisomycin group ( group MP+A) . The hearts were continuously perfused with K?R buffer for 105 min in group C. In group I∕R, the hearts were subjected to 45 min of global ischemia by stopping perfusion with K?R buffer, followed by 60 min of reperfusion by restoration of perfusion with K?R buffer. In group MP, the hearts were subjected to 45 min of global ischemia, followed by 10 min of reperfusion with K?R buffer containing 3?0 μmol∕L morphine and then by 50 min of reperfusion with K?R buffer. In group MP+A, the hearts were subjected to 45 min of global ischemia, followed by 10 min of reperfusion with K?R buffer containing 3?0 μmol∕L morphine and 1?0 μmol∕L anisomycin ( an activator of JNK and p38MAPK) and then by 50 min of reperfusion with K?R buffer. At 60 min of reperfusion, 8 hearts in each group were selected for measurement of the myocardial infarction and amount of creatine kinase?MB ( CK?MB) released from the myocardium, and the myocardial infarct size was calculated. At 20 min of reperfusion, 5 hearts in each group were selected to detect the expression of phosphorylated JNK ( p?JNK ) , phosphorylated p38MAPK ( p?p38MAPK) and cytochrome c ( Cyt c) in myocardial tissues ( by Western blot) and content of nicotinamide adenine dinucleotide ( NAD+) in myocardial tissues ( by spectrophotometry ) . Results Compared to group C, the myocardial infarct size and amount of CK?MB released from the myocardium were significantly increased, the expression of p?JNK, p?p38MAPK and Cyt c was significantly up?regulated, and the content of NAD+ was significantly decreased in I∕R, MP and MP+A groups ( P<0?05) . Compared to group I∕R, the myocardial infarct size and amount of CK?MB released from the myocardium were signifi?cantly decreased in MP and MP+A groups, and the expression of p?JNK, p?p38MAPK and Cyt c was sig?nificantly down?regulated, and the content of NAD+ was significantly increased in group MP (P<0?05). Compared to group MP , the myocardial infarct size and amount of CK?MB released from the myocardium were significantly increased, the expression of p?JNK, p?p38MAPK and Cyt c was significantly up?regula?ted, and the content of NAD+ was significantly decreased in group MP+A (P<0?05). Conclusion The mechanism by which morphine postconditioning attenuates myocardial I∕R injury is related to inhibition of activation of JNK and p38MAPK signaling pathways in rats.
