全肠外营养相关肝损害小鼠模型的建立

Parenteral nutrition induces liver disease in a mouse model

目的:为进一步研究肠外营养(PN)相关肝损害(PNALD)的患病机制及干预措施,建立有效的小鼠模型。方法:将20只小鼠随机分为对照组和模型组,对照组小鼠正常饮食、颈静脉置管后微量泵持续输注等渗盐水;模型组小鼠禁食后颈静脉置管,用微量泵持续输注PN液。1周后比较两组小鼠体重变化,血清生化指标以及肝组织学改变。结果:模型组小鼠体重明显低于对照组(P<0.05),直接胆红素、总胆红素和胆固醇均显著高于对照组(P<0.05),且肝组织在光镜下可见广泛性肝细胞脂肪变性,细胞质内出现大小不一的空泡,主要集中于中央静脉周围。脂肪变性评分为(3.1±0.5)分,显著高于对照组(1.0±0.0)分。结论:模型组小鼠与成人PNALD病人初期的临床和病理改变相似,可用于该病的患病机制,药物治疗疗效以及具体机制的观察和研究。

Objectives： This study was to ed liver disease. Methods： C57BL/6J female develop a mouse model of parenteral nutrition-associat- mice （aged 6 -8 weeks） were randomly assigned to parenteral nutrition or control group. A central venous catheter was inserted for intravenous infusion of a parenteral nutrition solution （model group ） or saline （control group ） for 7 days. Weights changes, hepatic biochemical tests and liver pathology were analyzed. Results： The model group gained signifi- cantly less weight than the control group （P 〈 0.05 ）. The model group showed significant increases in direct bilirubin, total bilirubin and serum cholesterol to the control group （ P 〈 0.05 ）. Livers in model group had severe, diffuse involvement of hepatocytes by macrovesicular and microvesicular steatosis. The pathological score were significantly higher in the model group than the control group （ 3.1 ± 0.5 and 1.0 ± 0.0 respectively, P 〈 0. 05 ）. Conclusion ： The model provides the opportunity to further investi-gate pathogenesis and treatment of parenteral nutrition-associated liver disease.