Prevention of mouse corneal allograft rejection by micromolecular compound J2

Abstract

To investigate the effects of J2 on the prevention of corneal allograft rejection in mice. Randomized control design was applied. One hundred C57BL/6 and thirty eight BALB/c mice were used as donors and recipients, respectively, to establish a corneal allograft model. These mice were randomly divided into A, B, C and D groups. There were 25 mice in each group. Group A, autograft control; Group B, allograft control (placebo was used in this group); Group C, allograft and treated with intraperitoneal ciclosporin A (CsA, 10 mg * kg(-1) * d(-1)) and Group D, allograft and treated with intraperitoneal J2 (15 mg * kg(-1) * d(-1)). All medications were applied on the day of transplantation and were continuously administrated for 12 days. Graft survival index, paraffin sections with HE staining and immunohistochemical staining of frozen sections were observed in each group 1, 2, 3 and 4 weeks after operation. IL-2 and IL-10 expression of cornea was detected by RT-PCR. One-Way ANOVO analysis was used to compare transplant survival time of the corneal allograft of each group. The average transplant survival time in the corneal allograft controls was (18.88 +/- 4.19) d. Treatment with J2 resulted in a significant increase of grafts' survival time (33.62 +/- 6.80) d (q = 0.85, P < 0.01). There was no significant difference between J2 and CsA groups. Histological examination showed that numerous lymphocytes infiltrated into the grafts 21 days after the operation in the control groups. Mild lymphocytes infiltration was found in both CsA and J2 groups. Immunohistochemical studies showed that large amount of CD4(+) and CD8(+) T-lymphocytes infiltrated into the grafts of the placebo group at 21 days. J2 and CsA groups only showed a small number of CD4(+) and CD8(+) T-lymphocytes in the grafts. RT-PCR showed that few IL-2 and IL-10 genes were expressed in the autologous transplantation group in the first week, and the expression of these two cytokines showed no significant increase during following three weeks. Both genes were expressed from the first week in the allogeneic transplantation group and significantly increased in the third week. Both genes were expressed from the first week in CsA and J2 group, expression was reduced in the second and third weeks. Expression of these cytokines in the fourth week was stronger than those in previous three weeks. J2 can inhibit corneal rejection in allograft mice model and its effect is similar to that of CsA.