Objective To investigate the impacts of sirolimus (SRL) on the survival time of graft and the differentiation and proliferation of regulatory T cell (Treg) of spleen in mouse heterotopic heart transplantation model.
Methods Male BALB/c→C57BL/6 mice cervical heterotopic heart transplantation model was established by Cuff method. The mice were divided into 3 groups randomly with 10 mice in each group. The control group received no treatment of special medicine after operation. Mice in SRL group were gavaged with SRL 10 mg/(kg·d) at 1-14 d after operation. Mice in ciclosporin (CsA) group were gavaged with CsA 30 mg/(kg·d)at 1-14 d after operation. The survival time of cardiac grafts were recorded. The spleen was procured after asystole of cardiac graft or 14 d after operation. Mononuclear cells were isolated and the proportion of CD4+CD25+Treg in CD4+ T cell(CD4+ CD25+ Treg%) were detected by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of Foxp3 messenger ribonucleic acid (mRNA) semi-quantitatively.
Results Compared with the control group, the survival time of cardiac grafts prolonged significantly in SRL and CsA group (all in P < 0.01), but no significant difference was observed between SRL and CsA group(P> 0.05). Compared with the control group, CD4+CD25+ Treg% significantly decreased in the spleen of CsA group and significantly increased in SRL group (all in P < 0.01). And significant difference was observed between SRL and CsA group (P < 0.01). Expression of Foxp3 mRNA of T lymphocyte in the spleen of SRL group was significantly higher than those in control and CsA group (P < 0.01). And expression of Foxp3 mRNA in control group was significantly higher than that in CsA group (P < 0.01).
Conclusions In mouse heart transplantation model, SRL can prolong the survival time of graft and promote the proliferation and growth of CD4+ CD25+ Treg to facilitate the establishment of immune tolerance.
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