中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (53): 9888-9892.doi: 10.3969/j.issn.1673-8225.2010.53.002

• 心肺移植 heart-lung transplantation • 上一篇    下一篇

过氧化物酶体增殖物激活受体γ在肺移植后闭塞性细支气管炎中的表达

刘宏旭1，王阁浜1，刘  洋2，许  顺1，张  林1   

  1. 1中国医科大学  附属第一医院胸外科，辽宁省沈阳市  110001；2中国医科大学基础医学院病理教研室，辽宁省沈阳市 110001
  • 出版日期:2010-12-31 发布日期:2010-12-31
  • 作者简介:刘宏旭☆，男，1972年生，辽宁省清原县人，满族，2003年中国医科大学毕业，博士，教授，博士生导师，主要从事肺移植后闭塞性细支气管炎发生机制方面的研究 hongxuliu@yahoo.com
  • 基金资助:

    国家自然科学基金项目(30700821),课题名称过氧化物酶体增殖物激活受体γ抑制肺移植术后闭塞性细支气管炎的作用机制。

Expression of peroxisome proliferator activated receptor gamma in obliterative bronchiolitis following lung transplantation

Liu Hong-xu1, Wang Ge-bang1, Liu Yang2, Xu Shun1, Zhang Lin1   

  1. 1 Department of Thoracic Surgery, First Affiliated Hospital, 2 Deparment of Pathology, Basic Medical College, China Medical University, Shenyang  110001, Liaoning Province, China
  • Online:2010-12-31 Published:2010-12-31
  • About author:Liu Hong-xu☆, Doctor, Professor, Doctoral supervisor, Department of Thoracic Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China hongxuliu@yahoo.com
  • Supported by:

    the National Natural Science Foundation of China, No. 30700821*

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摘要：

背景：过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptor，PPARγ)具有抑制组织纤维化和免疫调节的作用；但对其在实体器官移植方面的作用了解很少，而且它可能是抑制排斥反应的理想因子。
目的：通过检测过PPARγ在肺移植术后闭塞性细支气管炎中的表达情况，以探讨其作用机制。
方法：小鼠异位气管移植后，应用免疫组化染色检测PPARγ在移植后不同时期的定位；RT-PCR检测移植气管PPARγ mRNA表达情况。原代培养气道纤维母细胞，经转化生长因子β1(5 mg/L)处理后，于不同时间点采用RT-PCR法检测PPARγ mRNA表达；并于特定时间加入转化生长因子β1(5 mg/L)或PPARγ配体-罗格列酮(10 mmol/L)处理后，经Western Blot检测肌纤维母细胞的标志物α-平滑肌肌动蛋白原的表达。
结果与结论：PPARγ于移植后的炎性期定位于炎性细胞核内；而纤维增生期则定位于纤维细胞内。异位移植气管组织匀浆检测到PPARγmRNA含量明显下降。同样，培养的肺纤维母细胞经转化生长因子β1处理后PPARγmRNA含量也明显下降；而加入罗格列酮则能抑制转化生长因子β1诱导的α-平滑肌肌动蛋白原产生。提示，PPARγ表达的降低可能是肺移植后发生闭塞性细支气管炎的重要因素之一；而激活PPARγ能够抑制转化生长因子β1诱导产生的肌纤维母细胞分化。

关键词: 细支气管炎, 闭塞性, PPAR&gamma, 表达, 转化生长因子&beta, 1, 肌纤维母细胞

Abstract:

BACKGROUND: Peroxisome proliferator activated receptor γ (PPAR γ) plays some roles in inhibiting tissue fibrosis and modulating immune activity. However, little is known about its function in solid organ transplantations. It might be an ideal factor for the inhibition of rejection response.
OBJECTIVE: In order to investigate the mechanism of PPAR γ, we detected its expression in obliterative bronchiolitis after pulmonary transplantation.
METHODS: After ectopic tracheal transplantation in mice, immunohistochemistry staining was employed to detect the location of PPAR γ in different kinds of cells at different stages of post-transplantation animals. The expression of PPAR γ mRNA in transplanted trachea was analyzed with RT-PCR. Airway fibroblasts was primarily cultured and treated with transforming growth factor-β1 (TGF-β1) at 5 mg/L. At different time points, the expression of PPAR γ mRNA in fibroblasts was analyzed with RT-PCR. The expression of α-smooth muscle antigen-the marker of myofibroblasts was examined with Western blot after the fibroblasts were treated with TGFβ-1 (5 mg/L) or PPAR γ ligand-Rosiglitazone (10 mmol/L) at specific time interval. The expression of α-smooth muscle antigen in cultured pulmonary fibroblasts was investigated by Western Blot.
RESULTS AND CONCLUSION: In the inflammatory stage of post-transplantation, PPAR γ was found in the inflammatory cells, while in the fibroblasts in the fibrous proliferation stage. Markedly dropped of mRNA of PPAR γ was detected in the tissue homogenate of transplanted trachea. In the same way, the amount of PPAR γ mRNA remarkably diminished after the cultivated pulmonary fibroblasts were treated with TGF-β1. The addition of PPAR γ ligand-rosiglitazone could inhibit the production of α-smooth muscle antigen induced with TGF-β1. The results demonstrated that decreased expression of PPAR γ could be one of the most important factors contributing to the development of obliterative bronchiolitis after pulmonary transplantation. The activation of PPARγ could inhibit the differentiation of myofibroblasts induced by TGF-β1.

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