| Background: The activated form of vitamin D, 1 a , 25-Dihydroxyvitamin D3(1,25(OH)2D3) has important effects on the growth and differentiation of many cell types, and intriguing immunoregulatory properties.The biological effects of 1 a , 25-Dihydroxyvitamin D3 are mediated by the VITAMIN D RECEPTOR(VDR),a member of the superfamily of nuclear hormone receptors expressed in T cells and antigen presenting cells(APCS). Recent studies in understanding 1 a , 25-Dihydroxyvitamin D3 and its analogs functions suggest a wider applicability of this hormone in the treatment of autoimmune diseases and allograft rejection.Treatment combining 1 a, 25-Dihydroxyvitamin D3 with CsA can significantly delay the rejection of allogeneic grafts and improves survival in comparison to those treated with alone,although the mechanism is still unclear.Therefore,in-depth research on 1 alpha-hydroxycholecalciferol is useful in studying the immunopathologic process of rejection and pave new ways for probe the corneal graft rejection.Interleukin-1a (IL-1a ) and Tumor necrosis factor-α (TNF-α ) are two key agents to attend the acute immune rejection in experiment penetrating keratoplasty in rat model and were reported recently that they can induce Langerhans cells(LC) from the periphery to the central regions of the cornea;Vascular endothelial growth factor (VEGF) is unique polypeptide angents to effect intima. VEGF can accelerate the growth of corneal neovascularization. The animal experiments indicated that 1 a, 25-Dihydroxyvitamin D3 can markely immunosuppress corneal LC migration, and prevent vascular growth of corneal allografts.Here we performed this experment to determine the relationship among 1,25(OH)2D3 and cytokines(IL-1α , TNF-α , VEGF) during the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rat.Objectives:1. To investigate the effect of 1,25(OH)2D3 on the LC migrationand corneal neovascularization(CNV) and the expressions of cytokines(IL-1 a , TNF-α , VEGF) on corneas in rat CNV models,and to analysis relationship in them.2. To study comparatively the immunosuppressive effect of 1,25(OH)2D3 and CsA,and its effect on LC migrating and corneal neovascularization on the corneal allografts during the acute immune rejection in experiment high risk penetrating keratoplasty in rat.Methods: High risk corneal transplantation were performed orthotopically from Wistar rats to SD rats' recipients. Animals were randomly assigned to five groups: group I were treated by 1 X 10-7mol/L (1 a , 25-Dihydroxyvitamin D3) (n=15); group II were treated by 1X 10-5mol/L( 1 a , 25-Dihydroxyvitamin D3)(n=14) ;group III were treated by (1 X 10-5mol/L) 1,25(OH)2D3 and CsA(n=14); group IV were treated by CsA(n=15); group V were treated by N.S(n=14). Treatment were began at the first day postoperatively. Mean survival times, neovascularization and rejection index were determined. The eyes of six rats were enucleated at random in different postoperative days. Cellular morphologic changes of corneal buttons were evaluated by electron microscope examination. The immunohistochemitry conbined computer-assisted image analysis were adopted to examine the expression and distribution of LC and cytokines (IL-1α , TNF-α , VEGF) in corneal grafts during the allograft acute immunological rejection. At the same time, the corneas of SD CNV rats were examined with above methods(Part one).Results: The existence of Langerhans cell in high-risk and acute rejected corneal buttons were observed when examined with electron microscopy.LC is capable of migrating from the periphery to the central regions of the cornea during the induce process and allograft rejection of SD CNV rats. The expressions of cytokines (IL-1α , TNF-α , VEGF) increased significantly during the induce process and allograft rejection on the epithelium, stromaand endothelium of cornea; The migrating of LC and corneal vascularization index and the expression of cytokines(IL-l a , TNF-α ) of the group treated with 1,25(OH)2D3 was m... |
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