Li Lin, Chen Shao-Hua, Zhang Yu, Yu Chao-Hui, Li Shu-Dan, Li You-Ming
Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hepatobiliary Pancreat Dis Int. 2006 Nov;5(4):560-3.
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.
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.
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).
HIF-1alpha mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.
过量饮酒可导致多器官损伤,其中酒精性肝病(ALD)最为常见。随着经济发展和生活水平提高,中国因酒精滥用导致的疾病发病率不断上升,但其发病机制仍不清楚。本研究旨在探讨缺氧在慢性ALD中的作用。
将28只雄性Sprague-Dawley大鼠随机分为对照组(n = 12),该组大鼠无特殊处理;实验组(n = 16),通过胃灌洗法每天给予10 ml/kg的56%(体积/体积)乙醇,持续24周。24周时,采集血样,然后处死大鼠。肝脏样本在-80℃下冷冻用于RT-PCR;取其他肝脏样本进行免疫组织化学染色。
随着饮酒时间延长,酒精组肝脏中缺氧诱导因子-1α(HIF-1α)mRNA的阳性表达率比对照组显著升高(P≤0.05)。位于细胞质中的HIF-1α蛋白在对照组中很少表达,但在酒精组中表达显著(P≤0.01)。
本研究中乙醇诱导的损伤激活了HIF-1αmRNA表达,提示缺氧参与了ALD的潜在发病机制。