谷胱甘肽防止幼兔全胃肠外营养所致肝损害

目的研究氧化损伤及凋亡在全胃肠外营养(TPN)相关肝损害机制中的作用,并探讨谷胱甘肽防止TPN相关肝损害的有效性。方法将35只出生后6～8天的新西兰兔分为3组:正常对照组(n=12,母乳喂养);PN组(n=12,全肠外营养组,持续静脉营养10天);PN+GSH组(n=11,全肠外营养+还原型谷胱甘肽20mg/kg·d)。10天后比较3组间肝功能、肝脏光镜和电镜病理变化、TUNEL法检测肝细胞凋亡以及肝组织丙二醛(MDA)含量。结果PN组血直接胆红素、胆汁酸均明显高于正常对照组和PN+GSH组(P<0.05)。PN+GSH组病理无胆管扩张和胆汁淤积表现,电镜超微结构变化与病理相符。PN组肝组织MDA含量及肝细胞凋亡阳性率明显高于对照组和PN+GSH组(P<0.05,P<0.01)。结论氧化损伤及凋亡在TPN相关肝损害机制中可能起着重要作用;谷胱甘肽可明显减轻TPN所致肝细胞损害,可能与其抗氧化、抗凋亡作用有关。

Experimental Study on Prevention of Total Parenteral Nutrition Associated Liver Injury by Glutathione

Objective To investigate the mechanisms of oxidative injury and apoptosis in total parenteral nutrition(TPN)associated hepatic dysfunction and observe the possible effectiveness of glutathione to alleviate such injury. Methods Thirty-five New Zealand rabbits(6-8 days old, weight 80-110 g)were divided into 3 groups: 12 in control group(maternal fed); 12 in PN group(TPN for 10 days); and 11 in GSH+PN group(TPN infusion plus glutathione for 10 days). After 10 days, blood biochemical analysis and the liver histological examination were performed, and the malondialdehyde(MDA)content in liver tissues and TUNEL positive hepatocytes were also determined. Results The serum levels of direct bilirubin and bile acid in PN group were significantly higher than those in control group and GSH+PN group(P < 0.05). No obvious cholestatic or steatosis histological changes were found in GSH+PN group. The electron microscopic appearances were according with the histological findings. TUNEL assays showed the apoptotic hepatocytes positive rate in PN group was the highest among 3 groups(P < 0.01). MDA value in PN group was higher than the other 2 groups(P < 0.05). Conclusions The study showed that oxidative stress and apoptosis may play important roles in TPN associated hepatic dysfunction, and glutathione can reduce this injury effectively depending on its antioxidative and anti-apoptotic activities.