中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (5): 824-827.doi: 10.3969/j.issn.1673-8225.2010.05.016

• 肝移植 liver transplantation • 上一篇    下一篇

环孢素联合转化生长因子β1质粒对肝移植大鼠免疫反应的影响

张  岩，陈曦海，纪艳超，翟  哲，吴  波   

  1. 哈尔滨医科大学附属第四医院普外科，黑龙江省哈尔滨市  150001
  • 出版日期:2010-01-29 发布日期:2010-01-29
  • 通讯作者: 吴 波，教授，硕士生导师，哈尔滨医科大学附属第四医院普外科，黑龙江省哈尔滨市 150001 xinxin9129@126.com
  • 作者简介:张 岩★，男，1975年生，黑龙江省哈尔滨市人，汉族，哈尔滨医科大学毕业，硕士，主要从事器官移植研究。 jbjsbr@126.com
  • 基金资助:

    黑龙江省攻关项目(2010G0252- 00）*，黑龙江省教育厅资助项目（项目编号11541147）*

Effects of cyclosporine combined with transforming growth factor beta 1 plasmid on rat immunological reaction following liver transplantation

Zhang Yan, Chen Xi-hai, Ji Yan-chao, Zhai Zhe, Wu Bo   

  1. Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin  150001, Heilongjiang Province, China
  • Online:2010-01-29 Published:2010-01-29
  • Contact: Wu Bo, Professor, Master’s supervisor, Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China xinxin9129@126.com
  • About author:Zhan Yan★, Master, Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China jbjsbr@126.com
  • Supported by:

     the Tackle Key Program of Heilongjiang Province, No. 2010G0252-00*; Program of Heilongjiang Educational Committee, No. 11541147*

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摘要：

背景：大多数肝移植患者会发生急性排斥或慢性排斥反应导致移植肝失功能，通过不同途径诱导特异性免疫耐受是解决肝移植排斥问题最理想的方法。
目的：以注射转化生长因子β1质粒的方法对大鼠肝移植进行处理，从基因方面分析转化生长因子β1与移植免疫排斥反应的关系。
方法：选用雄性Wistar大鼠30只为异基因肝移植供体，雄性SD大鼠10只为同基因肝移植供体。雄性SD大鼠40只为肝移植受体，以数字表法随机分为4组：同种基因移植组、同种异基因移植组、环孢素组、环孢素联合转化生长因子组。各组均采用改良Kamada二袖套法并加以改进建立稳定的大鼠原位肝移植模型。造模后，环孢素组给予环孢素1~5 d，环孢素联合转化生长因子组腹腔注射环孢素A 1~5 d，同时腹腔注射转化生长因子质粒0~2 d，其他两组不给予任何干预措施，记录大鼠生存时间。于移植后3，7，14，21，28 d进行病理学、混合淋巴细胞培养。
结果与结论：同种基因移植组、环孢素联合转化生长因子组大鼠生存时间均达60 d以上，明显高于同种异基因移植组、环孢素组(P < 0.05)。同种异基因移植组、环孢素组病理组织切片可见中-重度急性排斥反应，肝内炎细胞浸润较为明显，主要集中在汇管区；环孢素联合转化生长因子组移植肝内组织损伤程度明显减轻；同种基因移植组基本无排斥反应，接近正常肝组织。环孢素联合转化生长因子组混合淋巴细胞培养优于同种异基因移植组、环孢素组(P < 0.05)。结果提示环孢素联合局部注射转化生长因子β1质粒可明显减轻大鼠肝移植移植后得免疫排斥反应。

关键词: 转化生长因子&beta, 1质粒, 免疫排斥, 肝移植, 孢素素, 大鼠

Abstract:

BACKGROUND: Most patients who underwent liver transplantation would suffer acute rejection or transplanted liver failure resulted by chronic rejection, therefore, inducing specific immune tolerance via varied pathways is the ideal method to solve this problem.

OBJECTIVE: To treat rat transplanted liver by injecting transforming growth factor β1 (TGF-β1) plasmid, and to analyze the relationship between TGF-β1 and allograft rejection from gene level.
METHODS: A total of 30 male, Wistar rats were served as allogenic liver donors, and 10 male, SD rats served as syngeneic donors Totally 40 male SD rats were served as liver recipients, and divided into 4 groups by order number table: allogenic transplantation, syngeneic transplantation, ciclosporin, and ciclosporin plus TGF-β1 groups. In each group, rat orthotopic liver transplantation model was established by modified Kamada and improved two-cuff technique. After modeling, rats were received cyclosporine 1-5 days in the cyclosporine group, or intraperitoneal injected ciclosporin for 1-5 days, combined with TGF-β1 plasmid 0-2 days in the cyclosporine plus TGF-β1 group. No intervention was performed in the other groups. The survival time of rats were recorded, and the pathological changes was detected at days 3, 7, 14, 21, and 28 after transplantation, then the mixed lymphocyte culture was performed..

RESULTS AND CONCLUSION: The survival time of rats in syngeneic transplantation group and cyclosporine plus TGF-β1 group was more than 60 days, which was obviously greater than that of allogenic transplantation and cyclosporine groups (P < 0.05). The histopathologic slide showed that there was moderate and severe acute rejection, with evident intrahepatic inflammatory cell infiltration in the allogenic transplantation and cyclosporine groups. Few rejections were observed in the syngeneic transplantation group, which was close to the normal lever tissues. Mixed lymphocyte culture of the cyclosporine plus TGF-β1 group was superior to the syngeneic transplantation group or cyclosporine group (P < 0.05). The results demonstrated that cyclosporine combined with local injection of TGF-β1 plasmid can relieve post-transplant immune rejection.

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