The effect of blastocyst MHC gene transfection on the survival of mouse heart grafts / 中华器官移植杂志

ABSTRACT

Objective To investigate the effects of Blastocyst MHC gene transfection to coronary on the survival time of mouse heart grafts and the mechanism. Methods Inbred male Balb/c mice and C57BL/6 mice were selected as donors and recipients respectively, to construct mouse cervical heart transplantation models. In the control group, the donor hearts were perfused using the 0～4 ℃ St. ThomasⅡ solution; in the cyclosporine A (CsA) group, the donor hearts were perfused as same as the control's and received intraperitoneal injection of CsA (5 rng·g-1·d-1) after surgery; in the transfection group, the donor hearts were perfused using St. Thomas Ⅱ solution with Blastocyst MHC gene plasmid; in the combined treatment group, the donor hearts were perfused using St. Thomas Ⅱ solution with Blastocyst MHC gene plasmid and received intraperitoneal injection of CsA (5 mg·g-1·d-1) after surgery. The survival time of transplanted heart allografts were observed, and their histopathological changes and the degrees of coronary intimal hyperplasia were estimated.Blastocyst MHC gene mRNA expression levels were detected by real-time fluorescence quantitative RT-PCR. Flow cytometry was applied in assessment of the levels of CD4+ CD25+ regulatory T cells (Treg) and CD3+ CD8+ T cells. Results The survival time in the CsA group, transfection group and combined treatment group was significantly longer than in the control group (P＜0.05) and that in the combined treatment group was the longest, up to (20. 50 ± 5. 61) days. On the postoperative day 1 and 3, Blastocyst MHC gene mRNA expression level in the transfection group was significantly higher than that in the control group (P＜0.05). On the postoperative day 7, the degrees of rejection and coronary intimal hyperplasia in the combined treatment group were the lightest. On the postoperative day 7 the number of Tregs in the CsA group and the combined treatment group was significantly increased as compared with that in the control group (P＜0.05), but that of CD3 + CD8+ T cells in the CsA group and the combined treatment group was less than that in the control group (P＜0.05). Conclusion Blastocyst MHC gene transfection in mouse transplanted cardiac allograft can extend its survival time through upregulation of Treg and downregulation of CD3 + CD8 + T cells in the mice. The combination of Blastocyst MHC gene and CsA may exert the synergic effects.