双歧杆菌减轻肠外营养幼兔肝损害的实验研究

The protective effects of bifidobacteria on liver damage induced by PN in infant rabbits

目的长期肠外营养（PN）患儿容易发生肝损害并发症，如肝脂肪变、胆汁淤积，甚至肝衰竭，其机制仍不清楚，可能和肠屏障功能障碍有关。近来双歧杆菌作为一种益生菌，在调节肠道微环境、保护肝脏中的作用日益受到重视。本研究拟通过给PN幼兔添加双歧杆菌，探讨其保护机制。方法生后3周的新西兰种白兔27只，体重200-250g。分为3组，PN组10只，PN＋双歧杆菌组8只，对照组9只。双歧杆菌组每日经胃管注入丽珠肠乐溶液1ml／只（含青春双歧杆菌0．5×10^8），PN组注人生理盐水1ml／只。PN持续10d，取血测肝功能、内毒素水平；作肝脏组织病理分级评分；作回肠黏膜显微测量；作内脏组织匀浆和血培养观察细菌移位。结果双歧杆菌组幼兔肝功能明显改善，血清总胆红素和胆汁酸含量较PN组显著下降（P〈0．05）。病理切片显示双歧杆菌组幼兔肝小叶完整，细胞形态基本正常，个别存在轻度炎症细胞浸润和纤维组织增生。而PN组则出现明显肝细胞变性（主要为脂肪变性）、胆管增生和胆汁淤积。参照Loff肝脏病理学评分标准，显示PN组分值明显高于对照组和双歧杆菌组（P〈0．05），而双歧杆菌组和对照组比较差异无显著性意义（P〉0．05）。肠道病理切片的计算机显微测量结果显示，双歧杆菌组幼兔回肠绒毛高度、隐窝深度、绒毛面积显著高于PN组（P〈0．05），和对照组比较差异无显著性意义（P〉0．05）。PN组幼兔血浆内毒素水平显著升高（P〈0．001），双歧杆菌组内毒素水平处于正常范围。内脏组织、器官细菌培养结果显示，PN组幼兔肠菌移位率明显高于双歧杆菌组（P〈0．01）。结论双歧杆菌可能通过降低肠黏膜通透性，避免幼兔产生肠菌移位和内毒素血症，保护肝功能。

Objective To investigate the role of bifidobacteria （BiD in the liver damage induced by long term parenteral nutrition （PN）. Methods Three-week-old New Zealand white rabbits weighing 200-250 g were divided into three experimental groups： （ 1 ） Control group （n = 9） ; （2） PN group （n = 10） ; （3） PN ＋ Bif group （n = 8）. PN ＋ Bif rabbits were gavaged a solution of bifidobacteria（0. 5× 10^8/d） through oral-stomach catheter. At the 10th day, blood samples were collected for hepatic function and endotoxin detection. Hepatic tissues ware graded and scored according to the standard by Loft. Small bowel samples were assayed for morphometry. Blood and peripheral organ sites were cultured for bacteria transloeation. Results Serum level of total bilirubin and bile acid in PN was higher than that in PN ＋ Bif rabbits（P〈0. 05）. Histologically, hepatic lobules were almost normal with occasionally low-grade inflammatory cell infiltration and fibrous tissue proliferation in PN ＋ Bif groups while there were obvious hepatocyte degeneration, bile duct proliferation and cholestasis in PN rabbits. Compared with PN ＋ Bif group, PN rabbits demonstrated a significant decrease in the ileal villus height, crypt depth and villus area （P〈0. 05 ）. Moreover, serum endotoxin level in PN rabbits was significant higher than that of control or PN ＋ Bif rabbits（P〈0. 01）. In addition, PN rabbits had a higher bacterial translocation rate than that of PN ＋ Bif. Conclusions Bifidobacteria may play a protective role in liver damage induced by PN through decreasing gut permeability, reducing bacterial translocation, and alleviating endotoxemia.