title: Protective effects of magnesium against ischaemia-reperfusion injury through inhibition of P-selectin in rats.
abstract: 1. The leucocyte-mediated inflammatory response plays a pivotal role in ischaemia-reperfusion injury. P-Selectin and CD11b are important mediators for the recruitment of leucocytes into the endothelium. However, the time-course of changes in P-selectin and CD11b expression during reperfusion is not defined. Magnesium has been shown to have a protective role in reperfusion injury, but the mechanism of its action is not yet clear. 2. In the present study, 90 male Sprague-Dawley rats were randomized into three groups, namely a sham-operated group, an IR group (subjected to 45 min of coronary occlusion followed by reperfusion for up to 6 h) and an MgSO(4)-treated group, which received an infusion of MgSO(4) starting 30 min before occlusion and continuing until the onset of reperfusion. The expression of P-selectin on platelets and CD11b on leucocytes, endothelial P-selectin on cardiac microvessels and P-selectin mRNA in myocardial tissue were measured by flow cytometry, immunohistochemistry and reverse transcription-polymerase chain reaction, respectively, at different time points during reperfusion. The degree of myocardial necrosis and arrhythmia was assessed. 3. The present study shows that P-selectin expression on platelets and cardiac microvessels, P-selectin mRNA in myocardial tissue and CD11b expression on leucocytes in the IR group were significantly upregulated compared with the sham-operated group in a time-dependent manner during reperfusion. Treatment with MgSO(4) attenuated the upregulation of P-selectin expression, in addition to inhibiting myocardial necrosis and arrhythmia, but had no effect on CD11b expression on leucocytes. 4. These results suggest that the expression of P-selectin and CD11b is upregulated after reperfusion and magnesium pretreatment plays a cardioprotective role in ischaemia-reperfusion injury, possibly by inhibiting the upregulation of P-selectin expression.
authors.affiliation: Department of Cardiovascular Disease, The Second University Hospital, School of Medicine, ZheJiang University, Hangzhou, China. yingshq@yahoo.com.cn
authors.forename: Shu-Qin
authors.initials: SQ
authors.lastname: Ying
authors.forename: Lu
authors.initials: L
authors.lastname: Fang
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Xiang
authors.forename: Geng
authors.initials: G
authors.lastname: Xu
authors.forename: Jiang
authors.initials: J
authors.lastname: Shan
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Wang
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D019007:P-Selectin; D020011:Protective Agents; D012333:RNA, Messenger; D008278:Magnesium Sulfate