Protective effects of magnesium against ischaemia-reperfusion injury through inhibition of P-selectin in rats

Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1234-9. doi: 10.1111/j.1440-1681.2007.04697.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • CD11b Antigen / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Magnesium Sulfate / therapeutic use*
  • Male
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Protective Agents / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Up-Regulation / drug effects

Substances

  • CD11b Antigen
  • P-Selectin
  • Protective Agents
  • RNA, Messenger
  • Magnesium Sulfate