Huiying Zhang1, Minli Lv2, Jiantao Jia3, Zhongfu Zhao4, Lili Zhang3, Lina Lai5, Yanjun Wu6, Baohong Li3, Chen Li7, Jingquan Ji3, Xiaoxia Tian3, Yan Liu7, Xujiong Li7, Hui Pang6, Jianhong Guo8, Limin Wang9, Yimin Fan9, Cuiying Zhang9, Dewu Han8, Cheng Ji10. 1. Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China. Electronic address: zhanghy2001@163.com. 2. ICU of the Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China. 3. Pathophysiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China. 4. Institute of Hepatology, Changzhi Medical College, Changzhi 046000, Shanxi, China. 5. Pharmacology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China. 6. Laboratory of Microbiology and Immunology, Changzhi Medical College, Changzhi 046000, Shanxi, China. 7. Physiology Department, Changzhi Medical College, Changzhi 046000, Shanxi, China. 8. Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi, China. 9. Functional Laboratory, Changzhi Medical College, Changzhi 046000, Shanxi, China. 10. USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Abstract
OBJECTIVE: This study is to explore the role of 78 kD glucose-regulated protein (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats. METHODS: The rat model of liver cirrhosis and HPS were induced with multiple pathogenic factors. Hematoxylin and eosin (H & E) staining was performed to detect the pathological changes of the lung and liver tissues. The levels of alanine transferase (ALT), endotoxin, and tumor necrosis factor-α (TNF-α) in plasma and TNF-α and malondialdehyde (MDA) in lung tissues were detected. RT-PCR and Western blotting were conducted to detect the mRNA and protein expression levels of GRP78 in lungs. RESULTS: The plasma endotoxin level was gradually increased as HPS developed, and the mRNA and protein expression levels of GRP78 in lungs were also increased as the disease progressed. The levels of ALT and TNF-α in plasma and the contents of TNF-α and MDA in lung tissues were gradually increased along with the disease progression, with a strong positive correlation. Compared with controls, the plasma TNF-α level and the mRNA and protein expression levels of GRP78 in lung tissues were significantly higher in rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in lungs were significantly higher in rats with HPS than controls. CONCLUSIONS: The increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS, which may play an important role in the disease pathogenesis.
OBJECTIVE: This study is to explore the role of 78 kD glucose-regulated protein (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats. METHODS: The rat model of liver cirrhosis and HPS were induced with multiple pathogenic factors. Hematoxylin and eosin (H & E) staining was performed to detect the pathological changes of the lung and liver tissues. The levels of alanine transferase (ALT), endotoxin, and tumornecrosis factor-α (TNF-α) in plasma and TNF-α and malondialdehyde (MDA) in lung tissues were detected. RT-PCR and Western blotting were conducted to detect the mRNA and protein expression levels of GRP78 in lungs. RESULTS: The plasma endotoxin level was gradually increased as HPS developed, and the mRNA and protein expression levels of GRP78 in lungs were also increased as the disease progressed. The levels of ALT and TNF-α in plasma and the contents of TNF-α and MDA in lung tissues were gradually increased along with the disease progression, with a strong positive correlation. Compared with controls, the plasma TNF-α level and the mRNA and protein expression levels of GRP78 in lung tissues were significantly higher in rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in lungs were significantly higher in rats with HPS than controls. CONCLUSIONS: The increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS, which may play an important role in the disease pathogenesis.
Authors: Nejla Güngör; Jeroen L A Pennings; Ad M Knaapen; Roland K Chiu; Marco Peluso; Roger W L Godschalk; Frederik J Van Schooten Journal: Respir Res Date: 2010-02-25