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 .
ABSTRACT
Objective To in ve stigate the effects of advanced glycation end products (AGEs) on matrix metallop roteinase-2 (MMP-2) activity and its mRNA expression in renal cortex of rats. Methods Diabetic model of rats was induced by s treptozotocin. AGEs were prepared by incubation of rat serum protein with 0.5 mo l/L glucose. AGEs was administered intravenously to normal rats (AGEs group), an d native rat serum protein was given as negative control (negative group) and no rmal rats without treatment were as control (control group). AGEs content in ren al cortex and serum was quantified by ELISA, MMP-2 and TIMP-2 mRNA expressions were examined by RT-PCR and MMP-2 activity was measured by zymography. Results AGEs content increased significantly, MMP-2 mRNA expression descended and TIMP-2 mRNA expression ascended in renal cortex o f diabetic rats (all P