Objective: To investigate the therapeutic effect of ursolic acid on corneal transplant rejection in rats.
Methods: Using SD rats as donors and Wistar rats as recipients, 48 Wistar rats were randomly divided into 4 groups. Group A was the normal corneal control group, group B was autologous orthotopic corneal transplantation in Wistar rats, and groups C and D were allogeneic corneal transplantation between SD-Wistar rats. The intraperitoneal administration was performed on the day after the operation. Groups A, B, and C were given normal saline as blank control, and group D was given ursolic acid (UA) (20 mg·kg-1·d-1) for 12 consecutive days. According to the corneal rejection scoring system such as Larkin, the postoperative graft rejection was judged. Corneal graft survival time and graft survival were compared. The expression levels of IL-2, IFN-γ, NF-κBp65, VEGF and ICAM-1 in each group were detected 14 days after operation, and the corneal grafts were examined by histology and Western blot analysis.
RESULTS: The storage time of corneal grafts in group D was 29.12±9.58 d, compared with 9.67±2.16 d in group C, there was a significant difference between the two groups (P<0.01). The relative contents of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF in the corneal grafts of group D decreased significantly, while the protein content of IκB-α was higher on the 14th postoperative day. There was no obvious lymphocyte infiltration and neovascularization.
Conclusion: Ursolic acid, as a nuclear factor inhibitor of NF-κB, can inhibit the formation and rejection of corneal neovascularization, thereby significantly prolonging the survival time of corneal grafts in rats.