Role of HMGB1∕TLR4 signaling pathway in myocardial ischemia-reperfusion injury in rats
10.3760/cma.j.issn.0254-1416.2018.09.029
- VernacularTitle:HMGB1∕TLR4信号通路在大鼠心肌缺血再灌注损伤中的作用
- Author:
Jie XIA
1
;
Jiyang XUE
;
Hanwei GE
;
Wei LIN
;
Hanlei WANG
;
Qifeng ZHAO
Author Information
1. 325027,温州医科大学附属第二医院 育英儿童医院心胸外科 儿童心脏中心 温州医科大学心脏发育与转化研究所
- Keywords:
High mobility group proteins;
Toll-like receptor 4;
Myocardial reperfusion injury
- From:
Chinese Journal of Anesthesiology
2018;38(9):1141-1145
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of high-mobility group box 1 protein ( HMGB1)∕Toll-like receptor 4 ( TLR4) signaling pathway in myocardial ischemia-reperfusion ( I∕R) injury in rats. Meth-ods Fifty-four clean-grade healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 200-250 g, were divided into 3 groups ( n=18 each ) using a random number table method: sham operation group ( group Sham) , myocardial I∕R group ( group I∕R) and specific HMGB1 antibody group ( group H) . Myo-cardial I∕R was produced by 30-min occlusion of left anterior descending branch of coronary artery followed by 180-min reperfusion in anesthetized rats. Specific HMGB1 antibody 2 mg∕kg was injected through the femoral vein at 30 min of reperfusion in group H. Twelve rats in each group were randomly selected at 180 min of reperfusion, and blood samples were collected from the femoral vein for determination of plasma in-terleukin-6 ( IL-6) , IL-8, IL-12, tumor necrosis factor-alpha ( TNF-α) and cardiac troponin I ( cTnI ) concentrations. The rats were then sacrificed, hearts were removed and myocardial tissues were obtained forexamination of the pathological changes and for determination of the expression of intercellular adhesion mol-ecule 1 ( ICAM-1) and E-selectin ( by immunohistochemistry) , expression of TLR4 and NF-κB mRNA and protein (by quantitative real-time polymerase chain reaction or by Western blot), activities of glutathione peroxidase ( GSH-PX) , superoxide dismutase ( SOD) and myeloperoxidase ( MPO) and MDA content. Six rats were selected for measurement of the myocardial infarct volume, and the percentage of myocardial in-farct volume was calculated. Results Compared with group Sham, the serum concentrations of IL-6, IL-8, IL-12, TNF-α and cTnI, MPO activity and MDA content were significantly increased, the expression of ICAM-1, E-selectin, TLR4 and NF-κB protein and mRNA was up-regulated, activities of GSH-PX and SOD were decreased, and the percentage of myocardial infarct volume was increased in group I∕R ( P<0. 01) . Compared with group I∕R, the serum concentrations of IL-6, IL-8, IL-12, TNF-α and cTnI, MPO activity and MDA content were significantly decreased, the expression of ICAM-1, E-selectin, TLR4 and NF-κB protein and mRNA was down-regulated, activities of GSH-PX and SOD were increased, and the percentage of myocardial infarct volume was decreased in group H ( P<0. 01) . Conclusion HMGB1∕TLR4 signaling pathway is involved in myocardial I∕R injury in rats.
