摘要
目的探讨转化生长因子－β（ＴＧＦ－β）单克隆抗体对博莱霉素所致肺间质纤维化的作用。方法结合体内和体外实验，利用３Ｈ－胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入法和Ｎｏｒｔｈｅｒｎ杂交法。结果表明大鼠肺纤维化模型中肺泡巨噬细胞的条件培养基能促进成纤维细胞的增殖和胶原ｍＲＮＡ的表达。ＴＧＦ－β１单克隆抗体对其有抑制作用，同时亦能减轻肺组织的病变程度和胶原ｍＲＮＡ的表达。结论ＴＧＦ－β１单克隆抗体可部分地抑制成纤维细胞增殖和胶原合成。
Objective Transforming growth factorβ(TGFβ) plays an important role in the pathogenesis of interstitial lung fibrosis. It can stimulate indirectly the mitosis of lung fibroblasts (LFb) as well as the synthesis and disposition of extracellular matrix. The purpose of this study was to evaluate the effects of TGFβ monoclonal antibody on bleomycininduced interstitial pulmonary fibrosis. Method The effect of TGFβ monoclonal antibody to bleomycininduced pulmonary fibrosis in rat was studied either in vivo or in vitro. The proliferation of lung fibroblasts was studied by measuring the incorporation rate of 3HTdR. Northern hybridization was used to detect mRNA level of procollagen A1(Ⅰ) and procollagen A1(Ⅲ) in cultured LFbs and lung tissue. Result The results showed that the incubation supernatant of alveolar macrophages from rats with pulmonary fibrosis had the ability to stimulate fibroblast proliferation as well as their procollagen expression. The monoclonal antibody could inhibit the proliferation of LFbs in a concentrationdependent manner. The highest concentration, 100 μg/ml, of TGFβ antibody could inhibit incorporation rate from 1749±322 of the fibrosis group to only 833±277 (P<0.01). The mRNA level of procollagen Ⅰ and Ⅲ was decreased by 44% and 28% respectively after the antibody treatment. In vivo, procollagen Ⅰ and Ⅲ mRNA level were decreased by 40% and 12% after the administration of TGFβ antibody though it could only slightly alleviate the extent of fibrosis and alveolitis in lung tissue. Conclusion TGFβ is a key factor stimulating the proliferation and collagen synthesis. TGFβ antibody can partially neutralize its action. This may suggest that the antibody might become a new therapeutic choice for pulmonary fibrosis in the future.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
1997年第6期347-349,共3页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
卫生部课题基金
关键词
肺纤维化
治疗
TGF-B
单克隆抗体
Transforming growth factorβ Interstitial pulmonary fibrosis Antibody
