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
Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of ei...Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline.Monocrotaline-injected rats received either atRA (30 mg· kg-1· day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromornetry, respectively.Results The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7+4.3 mm Hg vs 15.1 ± 1.5 mm Hg and 38.5 ± 6.4 mm Hg vs 16.4 ± 2.0 mm Hg, P ＜ 0.01 ). MMP-1 mRNA overexpression was present on Day 14 (0.72 ± 0.15 vs 0.39 ± 0.08, P ＜ 0.01 ) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 ± 1.13 μg/mg vs 5.10 ± 0.91 μg/mg, P ＜ 0.05)and increased significantly on Days 21 and 28 compared with the control, atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 ± 0.70 μg/mg vs 7.96 ± 1.13 μg/mg and 7.77 ± 0.96 μg/mg vs 9.93 ± 1.27μg/mg, P ＜ 0.01 ) and the mean pulmonary artery pressure compared with the model group ( 19.6 ± 3.2 mm Hg vs 25.7 ± 4.3 mm Hg and 26.3 ± 4.6 mm Hg vs 38.5±6.4 mm Hg, P＜0.01).Conclusion atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.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Objective To determine whether all-trans retinoic acid (atR A) exerts an inhibitory effect on rats with pulmonary hypertension induced by monocrotaline.Methods All rats were given a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline.Monocrotaline-injected rats received either atRA (30 mg· kg-1· day-1) or saline through oral-gastro intubation. On Days 7, 14, 21, and 28 respectively after monocrotaline injection, cardiovascular catheters were inserted to examine the mean pulmonary artery pressure of rats in each group. Meanwhile, the matrix metalloproteinase-1 (MMP-1) mRNA expression and hydroxyproline content in the main pulmonary artery were determined by RT-PCR and chromornetry, respectively.Results The mean pulmonary artery pressure of rats in the model group increased significantly on day 21 and reached a peak on Day 28 compared with the control group (25.7+4.3 mm Hg vs 15.1 ± 1.5 mm Hg and 38.5 ± 6.4 mm Hg vs 16.4 ± 2.0 mm Hg, P ＜ 0.01 ). MMP-1 mRNA overexpression was present on Day 14 (0.72 ± 0.15 vs 0.39 ± 0.08, P ＜ 0.01 ) and was rapidly down-regulated on Day 21 and 28 compared with Day 14, but was still higher than that in the control. The hydroxyoroline content of the main pulmonary artery dropped significantly on Day 14 (4.01 ± 1.13 μg/mg vs 5.10 ± 0.91 μg/mg, P ＜ 0.05)and increased significantly on Days 21 and 28 compared with the control, atRA inhibited the MMP-1 mRNA overexpression from Day 14 to Day 28 and reduced the hydroxyproline content (5.59 ± 0.70 μg/mg vs 7.96 ± 1.13 μg/mg and 7.77 ± 0.96 μg/mg vs 9.93 ± 1.27μg/mg, P ＜ 0.01 ) and the mean pulmonary artery pressure compared with the model group ( 19.6 ± 3.2 mm Hg vs 25.7 ± 4.3 mm Hg and 26.3 ± 4.6 mm Hg vs 38.5±6.4 mm Hg, P＜0.01).Conclusion atRA inhibits MMP-1 overexpression and the accumulation of collagen, which might elicit favorable geometric remodeling in rat pulmonary hypertension induced by monocrotaline.
