摘要
目的观察雷公藤内酯醇(triptolide,TPT)对同种异体小鼠皮肤移植的影响,探讨其抗排斥反应的作用机制。方法采用BALB/c小鼠→C57BL/6小鼠背-背皮肤移植法建立模型,随机分为假手术组、模型组、TPT组(200μg·kg-1)、环孢素A(CsA)组(10mg·kg-1)、TPT+亚剂量CsA组(TPT 200μg·kg-1+CsA 5 mg·kg-1),腹腔注射给药10天。记录受体鼠移植皮片的存活时间,酶联免疫吸附法检测血浆中白细胞介素Ⅱ(IL-2)、IL-4、IL-10、γ-干扰素(IFN-γ)含量,流式细胞术分析脾脏CD4+CD25+T淋巴细胞亚群的比例。结果各给药组小鼠移植皮片的存活天数均有明显延长,与模型组相比差异均有统计学意义(P<0.01);TPT+CsA组的移植皮片存活天数比TPT组或CsA组均有显著延长(P<0.05或P<0.01)。与模型组相比,TPT+CsA组及TPT组均可明显减少血浆Th1类细胞因子(IL-2、IFN-γ)的表达(P<0.01),明显增高Th2类细胞因子(IL-4、IL-10)的表达(P<0.01)。与模型组相比,TPT+CsA组及TPT组均可明显增高脾脏CD4+CD25+T淋巴细胞的比例(P<0.01)。结论TPT通过影响Th1/Th2型细胞因子、诱导免疫耐受、刺激CD4+CD25+T淋巴细胞的表达等途径,抑制了同种异体小鼠皮肤移植的排斥反应。
Objective To investigate the anti-rejection effect of triptolide(TPT)on xenogenic skin transplantation in mice.Methods The tergal skin transplantation model was achieved by an operation(BALB/c mice as donors and C57 BL/6 mice as acceptors).Then acceptors were divided randomly into 5 groups,namely model,TPT(200μg·kg-1),ciclosporin A(CsA)(10 mg·kg-1),combination of TPT and CsA(TPT 200μg·kg-1 and CsA 5 mg·kg-1)and sham.All acceptor mice were administered intraperitoneally once a day for ten days.The survival days of skin graft were documented in all groups.The levels of IL-2,IL-4,IL-10 and IFN-γin plasma were detected by ELISA ten days after the operation.The quantity of CD4+CD25+T cells in spleen were analyzed by flow cytometry.Results The survival days of skin graft in groups administered with drugs were all significantly prolonged compared with that of model group(P<0.01).Combination of TPT and CsA group showed a longer survival days than TPT or CsA group(P<0.05 or P<0.01).Compared with those of model group,Th1 cytokines(IL-2 and IFN-γ)in plasma in groups treated with TPT or combination of TPT and CsA were significantly decreased.(P<0.01)while Th2 cytokines(IL-4 and IL-10)were significantly increased(P<0.01).The amount of CD4+CD25+T cells in spleen in groups administered with TPT or combination of TPT and CsA were all significantly increased compared with that of model group(P<0.01).Conclusion TPT has an immunosuppressive effect on mice with xenogenic skin transplantation.The effectiveness of TPT appears to be associated with balance of Th1/Th2 cytokines,induction of immune tolerance and stimulation of expression of CD4+CD25+T cells,etc.
作者
邢玉琪
张玉秋
张国斌
XING Yuqi;ZHANG Yuqiu;ZHANG Guobin(Department of Pharmacy,Tsinghua University Yuquan Hospital,Beijing 100040,China;Pharmacy College,He’nan University of Traditional Chinese Medicine,He’nan Zhengzhou 450046,China)
出处
《中国药物警戒》
2019年第9期523-527,549,共6页
Chinese Journal of Pharmacovigilance
