Esworthy R S, Aranda R, Martín M G, Doroshow J H, Binder S W, Chu F F
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G848-55. doi: 10.1152/ajpgi.2001.281.3.G848.
Glutathione peroxidase (GPX)-1 and gastrointestinal (GI) epithelium-specific GPX (GPX-GI), encoded by Gpx1 and Gpx2, provide most GPX activity in GI epithelium. Although homozygous mice deficient in either the Gpx1 or Gpx2 gene appeared to be normal under standard housing conditions, homozygous mice deficient in both genes, double-knockout (KO) mice, had symptoms and pathology consistent with inflammatory bowel disease. These symptoms included a high incidence of perianal ulceration, growth retardation that started around weaning, and hypothermia that resembled that observed in calorie-restricted mice, even though the double-KO mice in our study were allowed to eat ad libitum. The growth retardation and hypothermia were components of cachexia, which is fatal in a high percentage of mice. Histological examination revealed that the double-KO mice had a high incidence of mucosal inflammation in the ileum and colon but not in the jejunum. Elevated levels of myeloperoxidase activity and lipid hydroperoxides were also detected in colon mucosa of these homozygous double-KO mice. These results suggest that GPX is essential for the prevention of the inflammatory response in intestinal mucosa.
谷胱甘肽过氧化物酶（GPX）-1和胃肠道（GI）上皮特异性GPX（GPX-GI）分别由Gpx1和Gpx2编码，在胃肠道上皮中提供了大部分的GPX活性。尽管在标准饲养条件下，Gpx1或Gpx2基因纯合缺失的小鼠看起来正常，但两个基因均缺失的纯合小鼠，即双敲除（KO）小鼠，出现了与炎症性肠病一致的症状和病理表现。这些症状包括肛周溃疡的高发生率、断奶前后开始的生长迟缓以及体温过低，后者类似于在热量限制小鼠中观察到的情况，尽管我们研究中的双敲除小鼠可以自由进食。生长迟缓和体温过低是恶病质的组成部分，在高比例的小鼠中是致命的。组织学检查显示，双敲除小鼠在回肠和结肠中有高发生率的黏膜炎症，但空肠中没有。在这些纯合双敲除小鼠的结肠黏膜中还检测到髓过氧化物酶活性和脂质氢过氧化物水平升高。这些结果表明，GPX对于预防肠道黏膜的炎症反应至关重要。
