Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2012; 18(37): 5283-5288
Published online Oct 7, 2012. doi: 10.3748/wjg.v18.i37.5283
Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline on bile duct ligation induced liver fibrosis in rats
Lei Zhang, Lei-Ming Xu, Yuan-Wen Chen, Qian-Wen Ni, Min Zhou, Chun-Ying Qu, Yi Zhang
Lei Zhang, Lei-Ming Xu, Yuan-Wen Chen, Qian-Wen Ni, Min Zhou, Chun-Ying Qu, Yi Zhang, Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China
Author contributions: Zhang L, Xu LM, Chen YW designed research; Zhou M and Qu CY contributed new reagents/analytic tools; Zhang Y and Ni QW analyzed data; and Zhang L, Zhou M and Xu LM wrote the paper.
Supported by Grants from National Natural Science Foundation of China, No. 30971263 and No. 81170410 (to Chen YW); and Shanghai Pujiang Program, No. 10PJ1407600 (to Chen YW)
Correspondence to: Dr. Lei-Ming Xu, Chief Physician, Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China. leiming.xu@yahoo.com.cn
Telephone: +86-21-65790000 Fax: +86-21-65790000
Received: March 20, 2012
Revised: June 11, 2012
Accepted: June 15, 2012
Published online: October 7, 2012
Abstract

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 wk via 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 profibrogenic TGF-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 metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10 vs 14.16 ± 6.50, 2.02 ± 0.45 vs 10.00 ± 3.35, 2.91 ± 0.30 vs 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 attenuated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.

Keywords: N-acetyl-seryl-aspartyl-lysyl-proline; Liver fibrosis; Transformating growth factor-β1; α-smooth mucle actin; Bone morphological protein-7; Fibroblast specific protein-1; Epithelial-mesenchymal transition