Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2005; 11(16): 2438-2443
Published online Apr 28, 2005. doi: 10.3748/wjg.v11.i16.2438
Effects of augmentation of liver regeneration recombinant plasmid on rat hepatic fibrosis
Qing Li, Dian-Wu Liu, Li-Mei Zhang, Bing Zhu, Yu-Tong He, Yong-Hong Xiao
Qing Li, Dian-Wu Liu, Li-Mei Zhang, Bing Zhu, Yu-Tong He, Yong-Hong Xiao, Department of Epidemiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of Hebei Province, No. 302489
Correspondence to: Dr. Dian-Wu Liu, Department of Epidemiology, Hebei Medical University, 361 Zhongshan Donglu, Shijiazhuang 050017, Hebei Province, China. liudianw@hebmu.edu.cn
Fax: +86-311-6265531
Received: July 31, 2004
Revised: August 2, 2004
Accepted: September 24, 2004
Published online: April 28, 2005
Abstract

AIM: To investigate the effects of eukaryotic expression of plasmid on augmentation of liver regeneration (ALR) in rat hepatic fibrosis and to explore their mechanisms.

METHODS: Ten rats were randomly selected from 50 Wistar rats as normal control group. The rest were administered intraperitoneally with porcine serum twice weekly. After 8 wk, they were randomly divided into: model control group, colchicine group (Col), first ALR group (ALR1), second ALR group (ALR2). Then colchicine ALR recombinant plasmid were used to treat them respectively. At the end of the 4th wk, rats were killed. Serum indicators were detected and histopathological changes were graded. Expression of type I, III, collagen and TIMP-1 were detected by immunohisto-chemistry and expression of TIMP-1 mRNA was detected by semi-quantified RT-PCR.

RESULTS: The histologic examination showed that the degree of the rat hepatic fibrosis in two ALR groups was lower than those in model control group. Compared with model group, ALR significantly reduced the serum levels of ALT, AST, HA, LN, PCIII and IV (P<0.05). Immunohistochemical staining showed that expression of type I, III, collagen and TIMP-1 in two ALR groups was ameliorated dramatically compared with model group (I collagen: 6.94±1.42, 5.80±1.66 and 10.83±3.58 in ALR1, ALR2 and model groups, respectively; III collagen: 7.18±1.95, 4.50±1.67 and 10.25±2.61, respectively; TIMP-1: 0.39±0.05, 0.20±0.06 and 0.53±0.12, respectively, P<0.05 or P<0.01). The expression level of TIMP-1 mRNA in the liver tissues was markedly decreased in two ALR groups compared with model group (TIMP-1 mRNA/β-actin: 0.89±0.08, 0.65±0.11 and 1.36±0.11 in ALR1, ALR2 and model groups respectively, P<0.01).

CONCLUSION: ALR recombinant plasmid has beneficial effects on rat hepatic fibrosis by enhancing regeneration of injured liver cells and inhibiting TIMP-1 expressions.

Keywords: Hepatic fibrosis; Rat; Augmentation of liver regeneration; Gene therapy; Tissue inhibitor of metalloproteinases-1