Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by regulation of transforming growth factor beta and connective tissue growth factor expression on rats with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate whether the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on transforming growth factor beta (TGF-beta1) and connective tissues growth factor (CTGF) was involved in AcSDKP's antifibrotic effect on the rats with silicosis.</p><p><b>METHODS</b>Rats were divided into 6 groups randomly, 10 rats in each group: Control of silicotic model: 1.0 ml normal sodium and was killed after 4 or 8 weeks; Silicotic model 1: 50 mg/ml silica suspension and was killed after 4 weeks; Silicotic model 2: 50 mg/ml silica suspension and was killed after 8 weeks; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 50 mg/ml silica suspension for 4 weeks, AcSDKP 800 microg/(kg x d) was administered into every rat and rats were killed at the 8 weeks; Preventing fibrosis treatment of AcSDKP: after AcSDKP [800 microg/(kg x d)] was administered into every rat for 48 hours, each rat was intratracheally instilled with 50 mg/ml silica suspension and rats were killed at the 8 weeks. Lung fibrosis in morphology was observed by HE staining. The expressions of TGF-beta1 and CTGF in lung were observed by immunohistochemistry. The mRNA expressions of TGF-beta1 and CTGF in lung were observed by real-time PCR.</p><p><b>RESULTS</b>In anti-fibrosis treatment of AcSDKP group, protein expression of TGF-beta1 and CTGF were (0.244 +/- 0.016) and (0.241 +/- 0.017) respectively, and significantly lower that those in the silicotic model 1 and 2 groups; mRNA expressions of TGF-beta1 and CTGF decreased, mRNA expressions of CTGF were significantly lower that those in the silicotic model 1 and 2 groups (P < 0.05); In preventing fibrosis treatment of AcSDKP group, protein expression and mRNA expression of TGF-beta1 were significantly lower that those in the silicotic model 2 group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP can decrease the expressions of TGF-beta1 and CTGF in lung tissues of the rats with experimentally induced pulmonary fibrosis.</p>

AcSDKP attenuates PDGF-induced cardiac fibroblasts proliferation and collagen expression: role of extracellular regulated protein kinase 1/2 pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of AcSDKP on platelet-derived growth factor (PDGF)-induced rat cardiac fibroblasts proliferation and collagen expression and explore the role of extracellular regulated protein kinase 1/2 (ERK1/2) pathway on this process.</p><p><b>METHODS</b>Metabolic activity of fibroblasts was determined by CCK-8. Cell cycle was detected by flow cytometry. Expressions of type I and type III collagen were measured by immunocytochemistry and Western blot. Expressions of phospho-ERK1/2 and ERK1/2 were detected by Western blot.</p><p><b>RESULT</b>10(-9) mol/L AcSDKP could significantly inhibit PDGF-induced cardiac fibroblasts proliferation, collagen expression and expressions of phospho-ERK1/2, while the protein levels of ERK1/2 were not significantly affected by AcSDKP.</p><p><b>CONCLUSION</b>AcSDKP could inhibit PDGF-induced cardiac fibroblasts proliferation and collagen expression through activation of phosphor-ERK1/2 pathway.</p>

Anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in lung of rat with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the collagen synthesis and expression in lung of rats with silicosis.</p><p><b>METHODS</b>Rats were divided into 6 groups randomly, 10 rats in each group: Control 1 of silicotic model: each rat was intratracheally instilled with 1 ml normal sodium and was killed at the fourth week; Control 2 of silicotic model: each rat was intratracheally instilled with 1 ml normal sodium and was killed at the eighth week; Silicotic model 1: each rat was intratracheally instilled with 1 ml silica suspension and was killed at the fourth week; Silicotic model 2: each rat was intratracheally instilled with 1 ml silica suspension and was killed at the eighth week; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 1 ml silica suspension for 4 weeks, AcSDKP 800 microg/(kgxd) was administered into every rat and rats were killed at the eighth week; Preventing fibrosis treatment of AcSDKP: after AcSDKP 800 microg/(kgxd) was administered into every rat for 48 hours, each rat was intratracheally instilled with 1 ml silica suspension and rats were killed at the eighth week. Lung fibrosis in morphology was observed by HE and VG staining. Collagen content was detected by hydroxyproline assay. The expression of type I and III collagen was evaluated by western blot.</p><p><b>RESULTS</b>Compared with those of silicotic model 1 and silicotic model 2 group, in anti-fibrosis treatment of AcSDKP group, the area of silicosis nodules decreased to 84.28% and 67.93%, the content of hydroxyproline decreased to 70.89% and 58.18%, the expression of type I collagen decreased to 71.08% and 58.13%, and expression of type III collagen decreased to 80.13% and 70.70%. Compared with those of silicotic model 2 group, in preventing fibrosis treatment of AcSDKP group, area of silicosis nodules decreased to 61.13%, content of hydroxyproline decreased to 60.27%, and expression of type I and type III collagen decreased to 40.13% and 65.77%.</p><p><b>CONCLUSION</b>AcSDKP could obviously inhibit the synthesis and expression of collagen in lung of rats with silicosis, which is possibly related with anti-fibrosis effect of AcSDKP.</p>