Usage of fingolimod combined with polyacetone system in the treatment of mouse kidney transplantation model

Abstract

A kidney transplantation model was established with mouse subjects, which was treated with the fingolimod (FTY720) combined with polyacetone (PCL) membrane controlled release system to analyze its therapeutic effect on kidney transplantation. 45 C57BL/6 (H-2b) mice were randomly enrolled into 3 groups, 9 in the Sham group did not receive any treatment, 18 in the model group and FTY720-PCL group, with 9 donors and recipients, respectively. The mice in model group were treated with kidney transplantation, and those in the FTY720-PCL group were treated with FTY720-PCL based on the model group. The three groups of mice were analyzed for serum creatinine (Scr), urine output, survival time of transplanted kidney (SToTK), overall survival time (OST), and the spleen tissue of the recipient mice. RT-PCR was used to detect the expression of IL-2 and ICAM-1 mRNA, and Western blot was used to detect the expression of CTLA4Ig and Fas/FasL protein. The pathological changes of the transplanted kidney were graded and evaluated according to the BanffSchema pathological diagnostic criteria. The results showed that the Scr level of the recipient mice in the FTY720-PCL group was greatly reduced (P < 0.05). Compared with the model group, urine output, SToTK, and OST were greatly increased (P < 0.05). The levels of interleukin 2 (IL-2) and intercellular adhesion molecule 1 (ICAM-1) mRNA in the spleen (P < 0.05) of the mice in the FTY720-PCL group were obviously reduced, the level of cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA4Ig) in the kidney was increased obviously, and factor related apoptosis (Fas) and factor related apoptosis ligand (FasL) (P < 0.05) levels dropped dramatically compared with the model group. The results of hematoxylin-eosin staining (HE staining) showed that the rejection rate of transplanted kidneys in the FTY720-PCL group was greatly reduced. In summary, FTY720-PCL membrane system can reduce the rejection rate of mouse kidney transplantation and prolong SToTK.