Sirolimus promotes differentiation and proliferation of regulatory T cells in mouse heart transplantation model / 器官移植

ABSTRACT

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.