AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was in...AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wkvia a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS:When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenicTGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col Ⅰ, Col Ⅲ, matrix metalloproteinase-2, tissue inhibitors of metallopro-teinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10vs 14.16 ± 6.50, 2.02 ± 0.45vs 10.00 ± 3.35, 2.91 ± 0.30vs 7.83 ± 1.10, 4.64 ± 1.25 vs 18.52 ± 7.61, 0.46 ± 0.16 vs 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION:Infusion of exogenous AcSDKP attenu-ated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.展开更多
In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive...In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.展开更多
To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac...To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac-SD_DK_DP were confirmed using flow cytometry,qRT-PCR,Western blots and fluorescence microscopy.The protective effects of Ac-SD_DK_DP on infarcted hearts were assessed in mice with myocardial infarction（MI）.The half-life of Ac-SD_DK_DP was prolonged to over 2 h from a few minutes that Ac-SDKP has.Compared with Ac-SDKP,the analog exhibited stronger inhibition on the differentiation of macrophages,expression of arginase I（ARG I） and TGF-β1 in mature macrophages,proliferation and secretion of collagen type I in cardiac fibroblasts.In MI mice mode,Ac-SD_DK_DP decreased collagen deposition and TGF-β1 expression in myocardium,thus improving the FS（%） to 23.0±7.8 compared with 11.2±6.2 in untreated mice and 11.7±5.3 in Ac-SDKP treated mice（P0.05）.This work shows that the Ac-SDKP analogue is potentially useful for protective treatment for heart failure post-MI.In addition,the anti-fibrosis mechanism of Ac-SDKP was correlated with the alternative activation（M2） of macrophages by assessing ARG I and TGF-β1,two important fibrosis-related molecules secreted in M2 macrophages.展开更多
基金Supported by Grants from National Natural Science Foundation of China, No. 30971263 and No. 81170410 (to Chen YW)Shanghai Pujiang Program, No. 10PJ1407600 (to Chen YW)
文摘AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wkvia a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS:When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenicTGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col Ⅰ, Col Ⅲ, matrix metalloproteinase-2, tissue inhibitors of metallopro-teinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10vs 14.16 ± 6.50, 2.02 ± 0.45vs 10.00 ± 3.35, 2.91 ± 0.30vs 7.83 ± 1.10, 4.64 ± 1.25 vs 18.52 ± 7.61, 0.46 ± 0.16 vs 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION:Infusion of exogenous AcSDKP attenu-ated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
文摘In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.
基金National Science and Technology Major Projects(Invention and Creation of New Drugs)of China 2011ZXJ09104-01BXijing project 9XJZT13M17
文摘To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D isomers.The biological activities of Ac-SD_DK_DP were confirmed using flow cytometry,qRT-PCR,Western blots and fluorescence microscopy.The protective effects of Ac-SD_DK_DP on infarcted hearts were assessed in mice with myocardial infarction（MI）.The half-life of Ac-SD_DK_DP was prolonged to over 2 h from a few minutes that Ac-SDKP has.Compared with Ac-SDKP,the analog exhibited stronger inhibition on the differentiation of macrophages,expression of arginase I（ARG I） and TGF-β1 in mature macrophages,proliferation and secretion of collagen type I in cardiac fibroblasts.In MI mice mode,Ac-SD_DK_DP decreased collagen deposition and TGF-β1 expression in myocardium,thus improving the FS（%） to 23.0±7.8 compared with 11.2±6.2 in untreated mice and 11.7±5.3 in Ac-SDKP treated mice（P0.05）.This work shows that the Ac-SDKP analogue is potentially useful for protective treatment for heart failure post-MI.In addition,the anti-fibrosis mechanism of Ac-SDKP was correlated with the alternative activation（M2） of macrophages by assessing ARG I and TGF-β1,two important fibrosis-related molecules secreted in M2 macrophages.
