Protective Effects of Magnesium Against Ischaemia–reperfusion Injury Through Inhibition of P‐selectin in Rats

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.