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新免疫抑制剂 F90 4是吸水链霉菌 (Streptomyceshygroscopicus) FC90 4产生的三烯大环内酯化合物 ,化学结构研究证实它与新型强效免疫抑制剂西罗莫司 (sirolimus,rapamycin)同质。体外免疫学试验显示F90 4能抑制 PHA诱导的 T淋巴细胞转化 ,抑制作用较环孢素 (Cs A)强约 10 0倍 ,IC5 0 <0 .1nmol/ L;抑制Con A诱导的 T淋巴细胞转化 ,抑制作用同 Cs A相当 ,IC5 0 1～ 10 nmol/ L;F90 4还能抑制 L PS诱导的 Ca2 +不依赖的 B细胞转化 ,IC5 0 1nmol/ L,Cs A的抑制作用则极其微弱。F90 4腹腔注射给药能显著抑制鼠迟发型超敏反应 ,ED5 0 2 mg/ kg,至少比 Cs A强 15倍 ;使鼠胸腺明显萎缩 ED5 0 0 .3mg/ kg,比 Cs A强 10 0倍 ;显著抑制鼠局部移植物抗宿主反应 ED5 0 3mg/ kg,至少比 Cs A强 10倍。结果提示 F90 4是优于 Cs A的强效免疫抑制剂
The new immunosuppressant, F90 4, is a triene macrolide compound produced by Streptomyces hygroscopicus FC90 4. Its chemical structure has been confirmed to be homogeneous with sirolimus (rapamycin), a potent and potent immunosuppressant. In vitro immunological experiments showed that F90 4 could inhibit the PHA-induced T lymphocyte transformation, the inhibitory effect was about 10 times stronger than that of CsA, IC50 <0.1 nmol / L; the inhibition of Con A-induced T lymphocytes The results showed that F90 4 could inhibit LPS-induced Ca 2+ -independent B cell transformation. The inhibitory effect of IC 50 1 nmol / L and Cs A was extremely weak . F90 4 intraperitoneal injection can significantly inhibit the delayed-type hypersensitivity in mice, ED5 0 2 mg / kg, at least 15 times stronger than Cs A; rat thymus significantly atrophy ED5 0 0 .3mg / kg, stronger than Cs A 10 Fold; significant inhibition of rat partial graft versus host response ED50 0mg / kg, at least 10 times stronger than CsA. The results suggest that F904 is a potent immunosuppressive agent that is superior to CsA