雷帕霉素对大鼠佐剂性关节炎的防治作用及其机理研究

EffectsofRapamycininPreventingandCuringAdjuvantArthiritisinRatsandItsMechanismofAction

本文研究了雷帕霉素（ｒａｐａｍｙｃｉｎ，ＲＰＭ）对大鼠佐剂性关节炎的作用，证明ＲＰＭ１０～５０ｍｇ／ｋｇ腹腔注射（ｉｐ）能完全预防弗氏完全佐剂（ＦＣＡ）所致大鼠关节继发肿胀的发生，对ＦＣＡ所致大鼠急性期原发性肿胀，环孢菌素Ａ（ＣｓＡ）效果优于ＲＰＭ，但ＣｓＡ停药不久即发生反跳。对继发肿胀的关节，ＲＰＭ５０ｍｇ／ｋｇｉｐ也显示了良好的治疗作用，且不发生反跳。Ｌ９２９细胞结晶紫染色法测得：关节炎大鼠腹腔巨噬细胞（ＭΦ）产生的肿瘤坏死因子α（ＴＮＦα）浓度显著升高，ＲＰＭ体内、外给药，均可抑制关节炎大鼠腹腔ＭΦ产生ＴＮＦα。２５ｍｇ／ｋｇ的ＲＰＭ预防和治疗给药，均可抑制关节炎大鼠的迟发型超敏（ＤＴＨ）反应。结果表明：ＲＰＭ对大鼠佐剂性关节炎的防治作用可能与其抑制ＴＮＦα的产生和ＤＴＨ反应有关。

Inpresentstudy,Rapamycin(RPM),ananotherpotentimmunosuppressant,showeditsactiontopreventtheonsetofadjuvantarthritis(AA)inratsatadoserangeof1to5mg/kgadministratedwithinthefirst10daysafterthediseaseinductionAlthoughCsAcouldpreventtheonsetofthediseaseandshowedmorepotenteffectsintheacutephase,thediseasewasreboundinthelatterphaseRPMalsosuccessfullyreducedpawedemaofestablishedadjuvantarthritisinratsatdoseof5mg/kggivenfor10daysfromday14today23CsAshowedsomeeffectsonthediseaseatthedoseof50mg/kg,butreboundlatteragainTheconcentrationofTNFproducedbyratperitonealmacrophages(Ms)wasmeasuredinastandardcytotoxicityassayusingacelllineofL929ItwasfoundthatthelevelofTNFproducedby AAratswasmuchhigherthanthatofnormalratsRPMinhibitedtheproductionofTNFproducedbyAAratsinvitroandinvivo RPM,administratedforpreventionorfortreatmentofAAatthedoseof25mg/kg,causedasignificantreductionindelayedtypehypersensitivity(DTH)inAAratswithoutreboundThemechanismofRPMonAAmightberelatedtoitsinhibitoryeffectontheproductionofTNFandthereductionof