Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2007; 13(25): 3500-3507
Published online Jul 7, 2007. doi: 10.3748/wjg.v13.i25.3500
Multiple pathogenic factor-induced complications of cirrhosis in rats: A new model of hepatopulmonary syndrome with intestinal endotoxemia
Hui-Ying Zhang, De-Wu Han, Zhong-Fu Zhao, Ming-She Liu, Yan-Jun Wu, Xian-Ming Chen, Cheng Ji
Hui-Ying Zhang, Zhong-Fu Zhao, Ming-She Liu, Yan-Jun Wu, Department of pathophysiology, Changzhi Medical College, Changzhi 046000, Shanxi Province, China
De-Wu Han, Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Xian-Ming Chen, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, United States
Cheng Ji, Department of Medicine, University of Southern California, Los Angeles, CA 90033, United States
Author contributions: All authors contributed equally to the work.
Supported by awards to University Academic Leaders granted by the Government of Shanxi Province of China to Hui-Ying Zhang and partially by the National Institute of Alcohol Abuse and Alcoholism of United States, grant R01 AA014428 to Cheng Ji
Correspondence to: De-Wu Han, Professor, MD, Director of Institute of Hepatology, Shanxi Medical University, 86 Xin jian Nan Road, Taiyuan 030001, Shanxi Province, China. smuhan@public.ty.sx.cn
Telephone: +86-351-4690082 Fax: +86-351-4690865
Received: March 19, 2007
Revised: March 20, 2007
Accepted: April 16, 2007
Published online: July 7, 2007
Abstract

AIM: To develop and characterize a practical model of Hepatopulmonary syndrome (HPS) in rats.

METHODS: The experimental animals were randomized into five feeding groups: (1) control (fed standard diet), (2) control plus intraperitoneal injection with lipopolysaccharide (LPS), (3) cirrhosis (fed a diet of maize flour, lard, cholesterol, and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4) oil solution), (4) cirrhosis plus LPS, and (5) cirrhosis plus glycine and LPS. The blood, liver and lung tissues of rats were sampled for analysis and characterization. Technetium 99m-labeled macroaggregated albumin (Tc99m-MAA) was used to test the dilatation of pulmonary microvasculature.

RESULTS: Typical cirrhosis and subsequent hepato-pulmonary syndrome was observed in the cirrhosis groups after an 8 wk feeding period. In rats with cirrhosis, there were a decreased PaO2 and PaCO2 in arterial blood, markedly decreased arterial O2 content, a significantly increased alveolar to arterial oxygen gradient, an increased number of bacterial translocated within mesenteric lymph node, a significant higher level of LPS and tumor necrosis factor-α (TNF-α) in plasma, and a significant greater ratio of Tc99m-MAA brain-over-lung radioactivity. After LPS administration in rats with cirrhosis, various pathological parameters got worse and pulmonary edema formed. The predisposition of glycine antagonized the effects of LPS and significantly alleviated various pathological alterations.

CONCLUSION: The results suggest that: (1) a characte-ristic rat model of HPS can be non-invasively induced by multiple pathogenic factors including high fat diet, alcohol, cholesterol and CCl4; (2) this model can be used for study of hepatopulmonary syndrome and is clinically relevant; and (3) intestinal endotoxemia (IETM) and its accompanying cytokines, such as TNF-α, exert a crucial role in the pathogenesis of HPS in this model.

Keywords: Alcohol; Carbon tetrachloride; Endotoxin; High fat diet