Role Of TGF-β1 Signaling Pathway In Regulation Of ECM Reconstructive Disorder In Endotoxin Induced Lung Injury In Rats

ObjectivesTo investigate the the role of TGF-β1 signaling pathway in ECM reconstructive disorders and pulmonary fibrosis in acute lung injury fibrosis induced by LipopolySaccharide(LPS). To clarify the mechanism and provide theoretical proof to explore effective preventive and therapic methods in clinic.Methods56 male SD rats were randomly divided into 3 groups, normal group (n=16), LPS group (n=20) and LPS+TGF-β1 antibody group (n=20). LPS group (group L):a single intratracheal (5mg/kg)+intraperitoneal (5mg/kg) injection of LPS; LPS+TGF-β1 antibody group (group T):the TGF-β1 antibody (2μg/100g) were applied intravenously before LPS; normal group (group N): were applied normal saline (NS) intratracheal and intraperitoneal. All rats were killed after modeling 1,5,9,14 days respectively, blood and lung tissue samples were obtained to detect the Wet/Dry ratio (W/D), diffuse alverolar damage (DAD) score, hydroxyproline activity (Hpy), TGF-β1, MMP-2, TIMP-1.ResultsCompared with the group N, The lung W/D, DAD score, Hpy activity, TGF-β1, MMP-2 and TIMP-1 expression of group L were higher, all indexes were significant different (P<0.05) except W/D. All indexes in group T were higher than the group N, Hpy, MMP-2 and TIMP-1 were significantly different (P<0.05). Compared with group L, all indicators in group T decreased after the intervention of TGF-β1 antibodies, Hpy, TGF-β1 and TIMP-1 significantly lower (P<0.05). After modeling 1,5,9 d, MMP-2 expression were gradually increasing and reach to maximum in 9 d, and then declined; Though Hpy activity, TGF-β1 and TIMP-1 expression kept rising after modeling.ConclusionsMMPs/TIMPs imbalance and ECM reconstruction disorder mediated by TGF-β1 signaling pathway may be an important cause of fibrosis in endotoxin-induced lung injury; TGF-β1 antibody can partly reduce the fibrosis of lung injury, and revealed a protective effect.