Experimental Study On The Effects Of 1,25-Dihydroxyvitamin D₃ In Prebention Of Rat Corneal Transplantation Rejection

Objective: To investigate the effects of 1, 25-dihydroxyvitamin D3 in prevention of corneal transplantaion rejection and its possible mechanism.Methods: 45 SD rats as recipients were randomly divided into three groups: the autograft control group, the allograft control group and the allograft group. Routine penetrating keratoplasty (PKP) was performed. In the the allograft control group and the allograft group, 30 SD rats were used as recipients, and 15 Wistar rats were used as donors. And in the autograft group, 15 SD rats got their own autografts.After PKP, the control groups were given placebo only, and the allograft group was treated with 1, 25-dihydroxyvitamin D3 (1.0μg·kg^-1·d^-1). The drugs were delivered for 14 days beginning at the day of transplantation. All grafts were examined by operating microscopy everyday after transplantation. 5 SD rats in every group were killed respectively at the 14th day, 21st day, and 30th day postoperatively. Neovascularization and inflammation were evaluated with HE staining. ELISA assay was used to detect the contents of IL^-1β, IL-2, IL-8, and IL-10 in the peripheral blood. Flow cytometry was used to identify the kinetic variation of the peripheral T cell population and CD4+/CD8+ ratio.Results:1. The mean survival time (MST) of the autograft control group was (21.7±6.8) days; the MST of the allograft control group was merely (11.2±2.5) days; and the allograft group led to a statistically significant prolongation of the MST to (19.3±5.2) days (P < 0.01).2. The rejection index of the allograft group was less than the allograft control group in the 14th day, 21st day, and 30th day postoperatively (P < 0.01).3. The allograft group has less neovascularization and inflammation than the allograft control group.4. The level of expression of IL^-1β, IL-2, and IL-8 in the allograft group was markedly lower than these in the allograft control group, and IL-10 were higher in the allograft control group (P < 0.01).5. In comparing with the allograft control group, the peripheral CD4+cell and CD4+/CD8+ in the allograft group were decreased significantly, and CD8+ cell was increased(P < 0.01).Conclusion:1. 1, 25-dihydroxyvitamin D3 could prolong the survival time of corneal allografts. 2. 1, 25-dihydroxyvitamin D3 could inhibit the immune rejection of corneal transplantation.3. 1, 25-dihydroxyvitamin D3 could significantly inhibit the expressions of IL-1β, IL-2, IL-8 which were secreted by Th1 cells, and increased the expressions of IL-10 which were secreted by Th2 cells.4. 1, 25-dihydroxyvitamin D3 could obviously decrease the peripheral CD4⁺cell and CD4⁺/CD8⁺, and increase the peripheral CD8+cell. It is indicated that 1, 25-dihydroxyvitamin D3 could inhibit the lymphocyte activation.