Anti-rejection study in mice skin transplantation of a novel immunosuppressant SYL934 / 中国药理学通报

ABSTRACT

Aim To determine the effect of SYL934 , a novel immunosuppressant, on skin allograft rejec-tion. Methods HTRF-IP1 assay was used to evaluate the agonistic activity of SYL934-P, the active form of SYL934 in vivo, on S1P1 and S1P3 in vitro. SD rat peripheral blood lymphocytes ( PBL ) test and heart rate test was used to assess the in vivo immunosuppres-sive effect and heart rate effect of SYL934 . Mice skin graft transplantation experiment was used to observe the effect of SYL934 on skin allograft refection. ResultsSYL934-P selectively activated S1 P1 but not S1 P3 in vitro. Single orally administration of SD rats with SYL934 decreased the PBL significantly and played an obviously immunosuppressant role, but did not affect the heart rate. Daily orally administration of mice with SYL934 significantly increased the survival rate of al-lografts of skin slice in mice. Conclusion SYL934 has great selectivity in vitro and good activity in vivo, which indicated it potential use as an anti-rejection drug in skin transplantation.