Effect of simvastatin combined with aspirin on heart allograft / 实用医学杂志

ABSTRACT

Objective To observe the effects of simvastatin combined with aspirin on the heart allograft and detect its mechanism. Methods Heterotopic heart transplantation was performed from Wistar to Sprague-Dawley (SD) rats. All SD rats were randomly assigned to Sham; HT (heart transplantation); HT + simvastatin(HT + S);HT + aspirin (HT + A); HT + aspirin + simvastatin (HT + A + S) group at different time points (day 3, 7, 10, 15, 20, 30 and 40) after transplantation (n=20). eNOS expression was detected by immunohistochemical methods and NO levels was measured by Griess assay. Meanwhile , the analysis of CD4+CD25+Tregs was performed by flow cytometry and histological examination for pathological change of heart and vascular. Results Simvastatin combined with aspirin significantly prolonged the mean survival time of heart allografts in HT + A + S group to (39 ± 5.3) days (n = 19) and in HT group to (8 ± 1.2) days (n = 18) (P < 0.001); simvastatin combined with aspirin delayed pathological changes of the transplanted hearts and protected vascular damage; simvastatin combined with aspirin upregulated eNOS and enhanced NO secretion. The level of CD4+CD25+Tregs in the blood of HT + A + S rats was significantly increased (2.2 ± 0.5)%, (2.9 ± 0.8)%, (4.3 ± 1.0)%, (8.3 ± 1.7)% and (14.3 ± 3.7)% for sham, HT, HT + S, HT + A and HT + A + S group respectively, HT vs. HT + A (P < 0.05) or HT + A + S (P < 0.01). Conclusion Simvastatin combined with aspirin delays the development pathology of myocardial and vascular damage and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with activating CD4+ CD25+ Treg cells induction immune tolerance and enhancing vascular endothelial cell protection.