结缔组织生长因子与大鼠移植肺纤维化的关系

Connective tissue growth factor and pulmonary allograft fibrosis in rats

检测结缔组织生长因子(connective tissue growth factor,CTGF)在大鼠移植肺内的表达,并探讨其与移植肺纤维化的关系。方法:检测结缔组织生长因子(CTGF)在大鼠移植肺内的表达,并探讨其与移植肺纤维化的关系。方法:取20只Wister大鼠作为供体,20只SD大鼠作为受体,进行原位左肺移植。急性排斥反应组(AR)大鼠于术后1周处死,慢性排斥反应组(CR)大鼠于术后6周处死,均取其移植肺作标本,取正常Wister大鼠肺标本作对照组(NH),每组10只。测取并计算肺组织的湿/干重比值(W/T);采用HE及Van Gieson染色观察肺组织病理形态,并进行纤维化的半定量评分;采用免疫组织化学方法检测CTGF在肺组织中的表达。结果:肺的W/T比值逐步减小(AR vs.NH:3.48±0.47vs.4.67±0.51,P<0.05;CR vs.AR:2.85±0.52vs.3.48±0.47,P<0.05);移植肺组织显示:大量炎性细胞浸润、肺间质纤维化、肺泡结构破坏、阻塞性肺炎、肺实变,CR组较AR组更明显;纤维化评分,AR组明显高于NH组(0.98±0.47vs.0.00±0.00),CR组(2.35±0.52)明显高于AR组,(均P<0.01)。CTGF在移植肺组织中有明显表达,且CR组较AR组更高(P<0.01),而正常肺无表达。结论:CTGF表达与移植肺纤维化密切相关,且参与了移植肺纤维化的病理过程。

Objective To investigate the role of connective tissue growth factor （CTGF） in pulmonary allograft fibrosis in rats. Methods The lungs of 20 Wister rats were transplanted into 20 Sprague-Dawely （SD） rats. Ten allograft lungs were harvested 1 week postoperatively （acute rejection group, AR） ; the other 10 allografts were harvested 6 weeks postoperatively （chronic rejection group, CR ） ; and ten normal Wister rats served as a control group （normal lung, NL ）. Paraffin embedded sections of the harvested lung specimens were stained with hematoxylin and eosin （ HE ） , Van Gieson （VG） for the examination of tissue morphology under the microscope. The scores of lung fibrosis were measured and the wet/dry ratio of the lung specimens was evaluated. The CTGF expression was determined by immunnohistochemical method. Results The wet/dry ratios of lung decreased gradu-ally（AR group vs. control group： 3.48±0.47 vs. 4.67±0.51, P〈0.05; CR group vs. AR group： 2.85±0.52 vs. 3.48±0.47, P 〈 0.05）. The transplanted lungs showed massive lymphocytic infiltration, interstitial fibrosis, destroyed alveolus architecture, obliterative bronchiolitis, and lung tissue consolidation. These pathological changes were more severe in the CR group than in the AR group, but there were no such changes in the control group （scores of pulmonary fibrosis：NH, 0.00±0.00; AR, 0.98±0.47; CR, 2.35±0.52; AR vs. NH, P〈0.01; CR vs. AR, P〈0.01）. CTGF was not expressed in the normal rat lungs （0.00±0.00） ; however, it was detected in the lung allograft after the operation. The CTGF expression in the CR group was significantly higher than that in the AR group （ P 〈 0.01）. Conclusion The expression of CTGF protein is related to the transplanted pulmonary fibrosis, and is involved in the pathogenesis of transplanted pulmonary fibrosis.