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1、雷公藤多甙对急性移植物抗宿主病小鼠的作用作者:于艳秋,张义侠,金玉楠,卢晓梅,王巍,张海鹏【摘要】本研究应用雷公藤多甙防治小鼠急性移植物抗宿主病。对受致死量照射的C57BL/6受鼠,注入供鼠BABC/c骨髓与脾淋巴细胞的混合液,并给予雷公藤多甙、环孢素A、甲氨蝶呤处理。用免疫组织化学法、流式细胞术和ELISA法检测各组小鼠T淋巴细胞、黏附分子、细胞因子。结果表明:所有异基因对照组小鼠,在30天内死于aGVHD,而雷公藤多甙组(19/21)、环孢素A+甲氨蝶呤组(13/21)和雷公藤多甙+环孢素A组(17/21)的大部分小鼠存活时间超过了30天,并没有明显的aGVHD症状表现。雷公
2、藤多甙、环孢素A、甲氨蝶呤可明显降低皮肤、肺组织CD3+、CD4+、CD8+、CD11a+、CD18+细胞(P<0.05)和脾组织CD3+,CD4+,CD8+,CD4+CD11a+,CD4+CD18+,CD8+CD11a+,CD8+CD18+细胞(P<0.05)。而小肠组织CD3+、CD4+、CD8+细胞变化不明显(P>005)。同时,雷公藤多甙可降低受鼠血清中IL-2、TNFα浓度和脾组织IL-2、TNFα的mRNA的表达(P<0.05);上调血清中IL-10的水平(P<0.05),但对IL-4的作用不显著(P>0.05)。结论:雷公藤多甙
3、具有明显抗aGVHD作用并同时保留抗白血病效应,其作用机制与调节促炎/抑炎细胞因子的分泌和黏附分子的表达,以及抑制T淋巴细胞作用有关。【关键词】雷公藤多甙;移植物抗宿主病;T淋巴细胞;黏附分子;细胞因子 GlucosidorumTripterygiiTororum(GTT)isakindofChinesetraditionalmedicine(CTM),forthefirsttimeusedinChinaasanimmunoregulatoryagententofautoimmunologicaldiseasessuchasrheumatoidarthritis(RA)and
4、nephroticsyndrome.Ourpreviousexperimentshophocytes,inhibitthesecretionofIL-2andexpressionofIL-2R,doolecules(CD11a,CD18)onthesurfaceofTcells.AnditcanprolongthesurvivaltimeofallogenEictransplantedskin.Itseffectonanti-rejectionisethylprednisolone.And,thebinationofGTTshouchmorestrongereffect,indi
5、catingthatGTTcanmoderatelyorobviouslyinhibitthefunctionofTcellsandthesecretionofcytokines[1].Furthermore,GTTmayhaveanti-inflammatoryandanti-tumoreffects.Graft-Versus-Hostdisease(GVHD),especiallyacuteGraft-Versus-Hostdisease(aGVHD)isamajorlethalplicationafterbonemarroedtoadoptGTTorbineGTTechan
6、ism. MaterialsandMethods Mice DonormiceBALB/c(H-2d),female;syngenEIctransplantationrecipientmiceBALB/c(H-2d),male;allogeneictransplantationrecipientmiceC57BL/6(H-2b)male.AllofthemyofSciences). InductionofaGVHD Therecipientsreceivedin,SIMENZ,Primus,Germany)for6-8hoursbeforetransplantation
7、.BonemarroaleBALB/c(H-2d)edium.BothBALB/candC57BL/6recipientsarrophocytesviacaudalvein. Assignmentandprocess Aftertransplantation,therecipientslydividedintofollo.Theirfoodandicin(320mg/L)anderythromycin(250mg/L)inistratedl;inCsA+MTXgroupg/k