Sokol R J, Taylor S F, Devereaux M W, Khandwala R, Sondheimer N J, Shikes R H, Mierau G
Section of Pediatric Gastroenterology and Nutrition, University of Colorado School of Medicine, Denver, USA.
Am J Physiol. 1996 Apr;270(4 Pt 1):G691-700. doi: 10.1152/ajpgi.1996.270.4.G691.
Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.
长期接受肠外营养的婴儿常出现肝胆功能障碍；然而，导致肝损伤的潜在机制尚不清楚。我们推测氧化应激在肠外营养诱导的肝脏异常中起重要作用，并在大鼠模型中验证了这一假设。断乳雄性大鼠通过中心静脉导管接受8天的全肠外营养（TPN组），成对喂食大鼠饲料并放置中心静脉导管（假手术组），或随意喂食大鼠饲料（对照组）。TPN 8天后，与假手术组和对照组相比，血清丙氨酸转氨酶和胆酰甘氨酸水平升高，出现肝细胞脂肪变性，肝线粒体嵴内空间扩张，线粒体脂质体粒体脂质过氧化增加。TPN 5天后，肝脏谷胱甘肽水平降至对照值的16%；随后在TPN 8天后出现线粒体脂质过氧化和血清胆酰甘氨酸水平升高。假手术组和对照组大鼠在8天后未显示线粒体脂质过氧化或肝损伤的证据。从TPN溶液中去除焦亚硫酸盐并添加半胱氨酸盐酸盐或胆碱对这些结果没有重大影响。TPN大鼠的细菌移位没有增加。这些数据表明，谷胱甘肽耗竭和氧化应激是断乳大鼠TPN诱导的肝脏异常发病机制中的重要因素。
