CAJ | 학술논문

目的：探讨新型免疫抑制剂SYL934对皮肤移植排斥反应的影响。方法采用体外 HTRF-IP1( Homogeneous Time-Resolved Fluorescence-IP1)方法,检测SYL934的活性磷酸酯 SYL934-P 对鞘氨醇-1-磷酸1型受体( sphingosine-1-phosphate receptor 1, S1P1)及鞘氨醇-1-磷酸3型受体(sphingosine-1-phosphate receptor 3, S1P3)的激动活性,采用体内大鼠外周血淋巴细胞检测实验考察SYL934的体内免疫抑制作用,采用大鼠心率检测实验考察SYL934对心率的影响,通过小鼠异体皮肤移植实验考察SYL934对皮肤移植排斥反应的影响。结果 SYL934的活性磷酸酯 SYL934-P能够在体外选择性激动S1P1而非S1P3,单次灌胃给予SD大鼠SYL934能够明显降低大鼠外周血淋巴细胞数量,发挥明显的免疫抑制效应,而不会影响大鼠心率。每天灌胃给予小鼠SYL934可以明显提高小鼠皮肤移植模型中移植皮片的存活率。结论 SYL934具有较好的体内外生物活性,具有开发成为抗皮肤移植排斥反应药物的应用前景。
목적：탐토신형면역억제제SYL934대피부이식배척반응적영향。방법채용체외 HTRF-IP1( Homogeneous Time-Resolved Fluorescence-IP1)방법,검측SYL934적활성린산지 SYL934-P 대초안순-1-린산1형수체( sphingosine-1-phosphate receptor 1, S1P1)급초안순-1-린산3형수체(sphingosine-1-phosphate receptor 3, S1P3)적격동활성,채용체내대서외주혈림파세포검측실험고찰SYL934적체내면역억제작용,채용대서심솔검측실험고찰SYL934대심솔적영향,통과소서이체피부이식실험고찰SYL934대피부이식배척반응적영향。결과 SYL934적활성린산지 SYL934-P능구재체외선택성격동S1P1이비S1P3,단차관위급여SD대서SYL934능구명현강저대서외주혈림파세포수량,발휘명현적면역억제효응,이불회영향대서심솔。매천관위급여소서SYL934가이명현제고소서피부이식모형중이식피편적존활솔。결론 SYL934구유교호적체내외생물활성,구유개발성위항피부이식배척반응약물적응용전경。
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 <br> 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.