中国药物警戒 ›› 2019, Vol. 16 ›› Issue (9): 523-527.
DOI: 10.19803/j.1672-8629.2019.09.02

• 基础与临床研究 • 上一篇    下一篇

雷公藤内酯醇对小鼠皮肤移植排斥反应的影响

邢玉琪1, 张玉秋1, 张国斌2,*   

  1. 1 清华大学玉泉医院药剂科,北京 100040;
    2 河南中医药大学药学院,河南 郑州 450046
  • 收稿日期:2019-01-28 修回日期:2019-10-21 出版日期:2019-09-20 发布日期:2019-10-21
  • 通讯作者: *张国斌,男,博士,副教授,中药活性成分与免疫调节作用。E-mail: zgb@hactcm.edu.cn
  • 作者简介:邢玉琪,女,本科,主管药师,医院药学。

Anti-rejection Effect of Triptolide on Experimental Skin Transplantation in Mice

XING Yuqi1, ZHANG Yuqiu1, ZHANG Guobin2,*   

  1. 1 Department of Pharmacy, Tsinghua University Yuquan Hospital, Beijing 100040, China;
    2 Pharmacy College, He’nan University of Traditional Chinese Medicine, He’nan Zhengzhou 450046, China
  • Received:2019-01-28 Revised:2019-10-21 Online:2019-09-20 Published:2019-10-21

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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（200 μg·kg-1）、环孢素A（CsA）组（10 mg·kg-1）、TPT + 亚剂量CsA组（TPT 200 μg·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Thl/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。

关键词: 雷公藤内酯醇, 免疫抑制, 皮肤移植, Th1/Th2, CD4+CD25+ T淋巴细胞

Abstract: 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 ( 200 μg·kg-1) , ciclosporin A (CsA) ( 10 mg·kg-1) , combination of TPT and CsA (TPT 200 μg·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-γ in 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.

Key words: triptolide, immunosuppressive effect, skin transplantation, Th1/Th2, CD4+ CD25+ T cells

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