Regulatory effect of TGF-beta 1 antibodies on extracellular matrix reconstruction in rats with lung injury fibrosis / 医学研究生学报

ABSTRACT

Objective Transforming growth factor-β( TGF-β) can regulate the expressions of matrix metalloproteinase (MMP) and matrix metalloproteinase (TIMP) inhibitors, thus affecting the reconstruction of extracellular matrix (ECM) after lung in-jury.So far, little is known about the regulation of TGF-β1 and MMPs/TIMPs ratio in endotoxin-induced lung injury as well as about the exact mechanisms of ECM reconstruction disorders .This study was to investigate the effects of TGF-β1 antibodies on the expressions of MMP and TIMP inhibitors and lung injury fibrosis in rats with endotoxin-induced acute lung injury . Methods Fifty-six male SD rats were randomly divided into three groups, normal (n=16), LPS (n=20), and LPS+TGF-β1(L+T, n=20).The rats of the LPS and L+T groups received intraperitoneal and intra-tracheal injection of endotoxin to induce lung injury fibrosis , the latter intrave-nously injected with TGF-β1 antibodies previously .The normal rats received intra-tracheal and intra-abdominal injection of the same a-mount of saline.At 1, 5, 9 and 14 days after modeling, all the rats were killed and blood and lung tissue samples obtained to detect the wet/dry lung tissue ( W/D ) ratio, diffuse alveolar damage ( DAD) score, hydroxyproline activity ( Hpy) , and the expressions of TGF-β1 , MMP-2 and TIMP-1. Results The DAD score, Hpy ac-tivity, and expressions of TGF-β1 , MMP-2 and TIMP-1 were signifi-cantly higher in the LPS group than in the normal control ( P 0.05), and so were the DAD score, Hpy activity, MMP-2, and TIMP-1 in the L+T group than in the controls (P<0.05).Com-pared with the LPS group, Hpy, TGF-β1 and TIMP-1 were markedly decreased in the L +T group (P<0.05).The expression of MMP-2 was gradually increased at 1, 5 and 9 days after modeling , reaching the peak at 9 days and then beginning to decline .The Hpy activity, TGF-β1 and TIMP-1 expressions kept rising after modeling . Conclusion The MMP/TIMP imbalance and ECM reconstruc-tion disorders mediated by the TGF-β1 signaling pathway may be an important cause of fibrosis in endotoxin-induced lung injury . TGF-β1 antibodies can exert a protective effect by alleviating lung injury fibrosis .