国产雷帕霉素对小鼠淋巴细胞增殖和DTH、GVHR的免疫抑制作用  

The immunosuppressive effect of rapamycin on lymphocytic proliferation and DTH、GVHR

作　　者：夏国伟[1] 姜汉英[2] 夏穗生[2] 

机构地区：[1]上海医科大学华山医院泌尿科 [2]同济医科大学器官移植研究所,武汉430030

出　　处：《中华器官移植杂志》2000年第6期350-352,共3页Chinese Journal of Organ Transplantation

摘　　要：目的　开发研制国产雷帕霉素 (Rapamycin ,RPM) ,探讨其免疫抑制作用机理。 方法　观察 :(1)RPM对刀豆素A(ConA)诱导的小鼠脾细胞 (T淋巴细胞 )增殖的抑制作用 ;(2 )RPM对脂多糖 (Lps)诱导的小鼠脾细胞 (B淋巴细胞 )增殖的抑制作用 ;(3)RPM对二硝基氯苯 (DNCB)诱导的小鼠迟发性过敏反应 (DTH)的抑制作用 ;(4 )RPM对大鼠宿主抗移植物反应 (GVHR)的抑制作用。结果　 (1)RPM对T淋巴细胞增殖有显著抑制作用 ,IC50 =1nmol/L ,环孢素A(CsA)的IC50 =10nmol/L(P <0 .0 5 )。 (2 )RPM显著抑制B淋巴细胞增殖 ,其IC50 =1nmol/L ,CsA的IC50 >10nmol/L(P <0 .0 5 )。 (3)RPM对DTH的ED50 ≈ 1.8mg/kg ,CsA的ED50 >30mg/kg(P <0 .0 5 )。 (4 )RPM对GVHR的ED50 =3mg/kg ,CsA的ED50 >30mg/kg(P <0 .0 5 )。结论　RPM比CsA能更好地抑制小鼠T、B淋巴细胞增殖 ,二者具有协同效应。且RPM比CsA能更好地抑制DTH和GVHR。Objective To manufacture rapamycin (RPM) a new type immunosuppressant made in our country and investigate its immunosuppressive mechanism. Methods The effect of RPM on mouse splenocyte (Tc) proliferation induced by ConA, splenocyte (Bc) proliferation induced by LPS, DTH induced by DNCB and rat GVHR were studied. Results RPM obviously restrained the proliferation of Tc with IC 50 =1?nmol/L, significantly lower than IC 50 (10?nmol/L) of CsA ( P < 0.05 ). RPM evidently repressed the proliferation of Bc with IC 50 =1?nmol/L significantly lower than IC 50 >10?nmol/L of CsA ( P < 0.05 ). RPM inhibited murine DTH to DNCB with ED 50 = 1.8 ?mg/kg, significantly lower than ED 50 >30?mg/kg of CsA ( P < 0.05 ). RPM controlled rat's GVHR with ED 50 =3?mg/kg, significantly lower than ED 50 ≥30?mg/kg of CsA ( P < 0.05 ). Conclusions RPM can inhibit lymphocytic proliferation and DTH, GVHR more markedly than CsA and they have combined efforts.

关 键 词：免疫抑制剂 淋巴细胞增殖 DTH GVHR 雷帕霉素 

分 类 号：R979.5[医药卫生—药品]