Protective Effect Of Cyclosporine A On Myocardial Ischemia-Reperfusion Injury In Rat Hearts

Objective To observe the effect of cyclosporine A on myocardial ischemia-reperfusion injury(MIRI) in rat hearts,and to explore the mecha- nisms of protective effect.Methods Thirty-two SD rats were randomly divided into four groups.Sham group,ischemia-reperfusion group(I/R),CsA group and CsA +5-HD group(n=8).The rats in CsA and CsA+5-HD group were administered cyclosporine A 15mg·kg-1·day-1 by peritoneal injection for 5 days before surgery,while the rats were given to the same volume of normal saline in the Sham and I/R group.In CsA +5-HD group,the rats were injected 5-Hydroxydecanoic acid sodium salt(5-HD) 10mg·kg-1 30 minutes before surgery.The rats in Sham group did not undergo left anterior descending coronary artery occlusions as a control group,while the rats in other three groups were subjected to 30min left anterior descending coronary artery occlusions and were reperfused for 24 hours .Then the left ventricular samples of each group were collected for investigation. The changes of CD4~+ and CD3~+T cells were detected by immunofluorescence. The expressions of CaNmRNA were detected by PT-PCR and CaN protein were detected by ELISA. Myocardial tissue sections stained by HE were studied under light microscope.Results The number of CD4~+T cells in Sham group,I/R group,CsA group and CsA+5-HD group were (25.38±2.83),(43.88±2.47),(33.84±3.13)and(34.13±3.48).Compared with Sham group,more CD4~+T cells were detected in I/R group,CsA group and CsA +5-HD group (p<0.05),and less CD4~+T cells were detected in CsA group and CsA +5-HD group than those in I/R group(p<0.05).The number of CD3~+T cells in Sham group,I/R group,CsA group and CsA+5-HD group were (35.75±2.96),(62.13±3.56),(45.86±3.44)and(46.00±3.30). In I/R group,CsA group and CsA +5-HD group more CD3~+T cells were detected, compared with Sham group (p<0.05),and less CD3~+T cells were detected in CsA and CsA+5-HD group than those in I/R group(p<0.05).The CaN expressions by ELISA in Sham group,I/R group,CsA group and CsA+5-HD group were (12.16±1.37),(22.62±2.70),(17.19±1.93)and(17.51±2.15). The expressions of CaNmRNA by PT-PCR in Sham group,I/R group,CsA group and CsA+5-HD group were (0.97±0.05),(1.64±0.54),(1.06±0.05)and(1.10±0.04).Compared with Sham group,higher CaN and CaNmRNA were found in I/R group,CsA group and CsA +5-HD group (p<0.05),and less CaN and CaNmRNA were found in CsA group and CsA +5HD group than those in I/R group(p<0.05).Cardiac HE sections were observed under light microscope,more remarkable histopathologic changes and T cells infiltration in I / R group than those in sham group,less remarkable histopathologic changes and T cells infiltration in CSA group and 5-HD+CSA group than those in I/R group.Conclusion It was suggested that cyclosporine A might have protective effect on myocardial ischemia -reperfusion injury through inhibition of CD4~+T cell activation.