Is the hypoxia-inducible factor-1 alpha mRNA expression activated by ethanol-induced injury, the mechanism underlying alcoholic liver disease?
BACKGROUND
Excessive alcohol consumption can result in multiple organ injury, of which alcoholic liver disease (ALD) is the most common. With economic development and improvement of living standards, the incidence of diseases caused by alcohol abuse has been increasing in China, although its pathogenesis remains obscure. The aim of this study was to investigate the role of hypoxia in chronic ALD.


METHODS
Twenty-eight male Sprague-Dawley rats were randomized into a control group (n=12) with a normal history and an experimental group (n=16) fed with 10 ml/kg of 56% (vol/vol) ethanol once per day by gastric lavage for 24 weeks. At 24 weeks, blood samples were collected and then the rats were killed. Liver samples were frozen at -80 degrees C and used for RT-PCR; other liver samples were obtained for immunohistochemical staining.


RESULTS
When the period of alcohol consumption increased, the positive rate of expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (P < or = 0.05). The HIF-1alpha protein located in the cytoplasm was seldom expressed in the control group, but significantly in the alcohol group (P < or = 0.01).


CONCLUSIONS
HIF-1alpha mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.
Li
Lin
L
Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. liph@zj139.com
Chen
Shao-Hua
SH
Zhang
Yu
Y
Yu
Chao-Hui
CH
Li
Shu-Dan
SD
Li
You-Ming
YM
D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D000431:Ethanol