Original Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 14, 2009; 15(10): 1231-1236
Published online Mar 14, 2009. doi: 10.3748/wjg.15.1231
Role of cathepsin B-mediated apoptosis in fulminant hepatic failure in mice
Bing-Zhu Yan, Wei Wang, Li-Yan Chen, Man-Ru Bi, Yan-Jie Lu, Bao-Xin Li, Bao-Shan Yang
Bing-Zhu Yan, Wei Wang, Li-Yan Chen, Man-Ru Bi, Bao-Shan Yang, Department of Infectious Diseases, the Second Clinical Hospital of Harbin Medical University, Harbin 150086, China
Yan-Jie Lu, Bao-Xin Li, Department of Pharmacology, Harbin Medical University, Harbin 150086, China
Author contributions: Yan BZ and Yang BS designed the study; Yan BZ, Wang W, Chen LY, Bi MR performed the experiment and analyzed the data; Yan BZ wrote the paper; Lu YJ, Li BX assisted in the experiment.
Correspondence to: Bao-Shan Yang, Professor, Department of Infectious Diseases, the Second Clinical Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin 150086, China. baoshanyang@hotmail.com
Telephone: +86-451-86297509
Fax: +86-451-86605330
Received: December 26, 2008
Revised: February 10, 2009
Accepted: February 17, 2009
Published online: March 14, 2009
Abstract

AIM: To investigate the pathogenic role of cathepsin B and the protective effect of a cathepsin B inhibitor (CA-074Me) in fulminant hepatic failure in mice.

METHODS: LPS/D-Gal N was injected into mice of the model group to induce fulminant hepatic failure; the protected group was administered CA-074me for 30 min before LPS/D-Gal N treatment; the normal group was given isochoric physiologic saline. Liver tissue histopathology was determined with HE at 2, 4, 6 and 8 h after Lps/D-Gal injection. Hepatocyte apoptosis was examined by TUNEL method. The expression of cathepsin B in liver tissues was investigated by immunohistochemistry, Western blot and RT-PCR.

RESULTS: Compared with the normal group, massive typical hepatocyte apoptosis occurred in the model group; the number of apoptotic cells reached a maximum 6 h after injection. The apoptosis index (AI) in the protected group was clearly reduced (30.4 ± 2.8 vs 18.1 ± 2.0, P < 0.01 ). Cathepsin B activity was markedly increased in drug-treated mice compared with the normal group (P < 0.01). Incubation with LPS/D-Gal N at selected time points resulted in a time-dependent increase in cathepsin B activity, and reached a maximum by 8 h. The expression of cathepsin B was significantly decreased in the protected group (P < 0.01).

CONCLUSION: Cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury.

Keywords: Fulminant hepatic failure; Hepatocyte apoptosis; Cathepsin B; CA-074me