Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 7, 2012; 18(25): 3235-3249
Published online Jul 7, 2012. doi: 10.3748/wjg.v18.i25.3235
Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl4-treated mice
Xiao-Ling Wang, Dong-Wei Jia, Hui-Yang Liu, Xiao-Feng Yan, Ting-Jie Ye, Xu-Dong Hu, Bo-Qin Li, Yong-Liang Chen, Ping Liu
Xiao-Ling Wang, Dong-Wei Jia, Hui-Yang Liu, Xiao-Feng Yan, Ting-Jie Ye, Xu-Dong Hu, Department of Cell Biology, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 210203, China
Bo-Qin Li, Yong-Liang Chen, Department of Cell Biology, Experimental Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 210203, China
Ping Liu, E-institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai 210203, China
Ping Liu, Institution of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medical, Shanghai 210203, China
Author contributions: Liu P designed the research; Wang XL wrote the paper; Jia DW and Liu HY performed the research; Yan XF, Ye TJ, Hu XD, Li BQ and Chen YL contributed to the bone marrow transgenic technique.
Supported by National Natural Science Foundation of China, No. 30772758; and National Science and Technology Major Project of China, No. 2009ZX09311-003
Correspondence to: Liu Ping, MD, PhD, Chief, E-institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 210203, China. liuliver@online.sh.cn
Telephone: +86-21-51322059 Fax: +86-21-51322445
Received: November 4, 2011
Revised: March 29, 2012
Accepted: April 2, 2012
Published online: July 7, 2012
Abstract

AIM: To investigate the cellular mechanisms of action of Yiguanjian (YGJ) decoction in treatment of chronic hepatic injury.

METHODS: One group of mice was irradiated, and received enhanced green fluorescent protein (EGFP)-positive bone marrow transplants followed by 13 wk of CCl4 injection and 6 wk of oral YGJ administration. A second group of Institute for Cancer Research mice was treated with 13 wk of CCl4 injection and 6 wk of oral YGJ administration. Liver function, histological changes in the liver, and Hyp content were analyzed. The expression of α-smooth muscle actin (α-SMA), F4/80, albumin (Alb), EGFP, mitogen-activated protein kinase-2 (PKM2), Ki-67, α fetoprotein (AFP), monocyte chemotaxis protein-1 and CC chemokine receptor 2 were assayed.

RESULTS: As hepatic damage progressed, EGFP-positive marrow cells migrated into the liver and were mainly distributed along the fibrous septa. They showed a conspicuous coexpression of EGFP with α-SMA and F4/80 but no coexpression with Alb. Moreover, the expression of PKM2, AFP and Ki-67 was enhanced dynamically and steadily over the course of liver injury. YGJ abrogated the increases in the number of bone marrow-derived fibrogenic cells in the liver, inhibited expression of both progenitor and mature hepatocyte markers, and reduced fibrogenesis.

CONCLUSION: YGJ decoction improves liver fibrosis by inhibiting the migration of bone marrow cells into the liver as well as inhibiting their differentiation and suppressing the proliferation of both progenitors and hepatocytes in the injured liver.

Keywords: Yiguanjian decoction, Bone marrow transplantation, Hepatic progenitors, Hepatocytes, Hepatic injury