新生巴马小猪全肠外营养模型的建立及肠屏障功能研究

Establishment of total parenteral nutrition model and study on intestinal barrier function in newborn Bama mini-pig

目的为更好模拟儿科肠外营养相关并发症,拟用新生巴马小猪建立肠内及肠外营养相关模型。方法新生巴马小猪18只,分为肠内营养(enteral nutrition,EN)组和全肠外营养(total parenteral nutrition,TPN)组。EN组包括喂养1周(EN-1W,n=3)和喂养2周(EN-2W,n=3)小猪;TPN组包括肠外营养支持1周(TPN-1W,n=6)和肠外营养支持2周(TPN-2W,n=6)小猪。观察记录小猪体重和组织形态学;检测分析肝功能和肠屏障功能。结果造模期间TPN小猪全部存活,TPN-2W小猪肠外营养相关并发症较TPN-1W更明显。与EN-2W组对照相比,TPN-2W小猪的体重下降明显,差异有统计学意义(P<0.05)。TPN-2W小猪血清中的总胆红素、直接胆红素及胆汁酸含量明显高于EN-2W组,差异均有统计学意义(P<0.05)。肝脏形态学显示,TPN小猪肝脏门脉区有炎症细胞浸润并伴有肝细胞轻度脂肪变。与EN-2W组对照相比,TPN-2W小猪回肠绒毛萎缩变形、绒毛长度明显变短(P<0.05)、隐窝深度变浅(P<0.01),其肠通透性明显增加(P<0.05)。结论建立新生巴马小猪的TPN模型,模拟了婴幼儿肠外营养相关肝损害及肠屏障损伤等并发症,为研究儿科肠外营养相关并发症的发病机制提供了较好的动物模型。

Objective To better simulate parenteral nutrition-associated complications in pediatrics,establishment of enteral and parenteral nutrition-related models were planned with newborn Bama mini-pig.Methods Eighteen newborn Bama mini-pigs were divided into enteral nutrition(EN)groups and total parenteral nutrition(TPN)groups.EN groups were further divided into EN-1W(n=3)and EN-2W(n=3);and TPN groups were divided into TPN-1W(n=6)and TPN-2W(n=6).The weight and histomorphological changes of newborn Bama mini-pigs were observed.Liver function and intestinal barrier function were also detected and analyzed.Results During modeling,all Bama mini-pigs in TPN groups survived,the related complications of TPN-2W mini-pigs were more obvious than that of TPN-1W mini-pigs.Compared with EN-2W group,the weight of TPN-2W group decreased significantly(P<0.05).Serum total bilirubin,direct bilirubin,and bile acid levels in TPN-2W group were significantly higher than those in EN-2W group(P<0.05).The hepatic histomorphology of the TPN groups showed scattered portal inflammatory infiltration and mild hepatic steatosis.Compared with EN-2W group,the intestinal villi of the TPN-2W mini-pigs were atrophic and deformed,with significantly decreased villus length(P<0.05),and crypt depth(P<0.01),and significantly increased intestinal permeability(P<0.05).Conclusion An experimental model of total parenteral nutrition can be established using the newborn Bama mini-pigs,which can well simulate the parenteral nutrition-associated liver damage and intestinal barrier injury in infants and young children,thus providing a better animal model to study the pathogenesis of clinical parenteral nutrition-associated complications in pediatrics.