高胆红血素症动物模型的研究

Study of animal model of hyperbilirubinemia

目的建立稳定的存活周期长的高胆红素血症动物模型,以评价体外支持在人工肝及血液净化材料研究中的效能。方法将14头实验香猪随机分为四组,组Ⅰ3头给予颈静脉注射5%葡萄糖;组Ⅱ3头给予颈静脉注射1.2 g/kg D-Gal;组Ⅲ3头给予颈静脉注射0.2 g/kg D-Gal;组Ⅳ5头给予颈静脉注射0.2 g/kg D-Gal联合结扎胆管。对四组实验香猪定时采血分别检测不同时间段总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、直接胆红素(DBIL)等生化指标,凝血酶原时间(PT)、凝血酶原活动度(AT)、纤维蛋白原(FIB)、凝血酶时间(TT)等凝血指标,定时取肝组织进行光镜、电镜病理组织学检查,同时监测不同组别实验香猪的存活率。结果与组Ⅰ香猪相比,组Ⅱ香猪ALT、AST、TBIL和DBIL在给药第2天迅速上升,生存周期较短;组Ⅲ香猪在给药第2天ALT、AST和凝血指标上升,第3天逐渐恢复正常;组Ⅳ香猪TBIL和DBIL在给药后能保持相对稳定且生存周期较稳定。结论低剂量D-Gal联合结扎胆管能够建立稳定、成活率高的高胆红血素症动物模型,为临床研究提供实用可靠的动物模型。

Objective To establish a stable hyperbilirubinemia animal model with long survival cycle to evaluate the efficacy of in vitro support in the study of artificial liver and blood purification materials.Methods Fourteen experimental fragrant pigs were randomly divided into four groups.Three pigs in group I were injected with 5%glucose through jugular vein;three pigs in groupⅡwere injected with 1.2 g/kg D-Gal through jugular vein;three pigs in groupⅢwere injected with 0.2 g/kg D-Gal through jugular vein;five pigs in groupⅣwere injected with 0.2 g/kg D-Gal through jugular vein combined with ligation of the bile duct.Blood samples were taken from four groups of experimental fragrant pigs at regular intervals to detect biochemical indexes such as total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),direct bilirubin(DBIL),coagulation indexes such as prothrombin time(PT),prothrombin activity(AT),fibrinogen(FIB),thrombin time(TT).Liver tissues were taken at regular intervals for light and electron microscopic histopathological examination,at the same time,the survival rates of different groups of experimental fragrant pigs were monitored.Results Compared with groupⅠfragrant pigs,ALT,AST,TBIL and DBIL of groupⅡfragrant pigs increased rapidly on the second day of administration,and the survival cycle was short;the ALT,AST and coagulation indexes of fragrant pigs in group III increased on the second day of administration,and gradually returned to normal on the third day;in group IV,TBIL and DBIL of fragrant pigs remained relatively stable and their survival cycle was relatively stable after administration.Conclusion Low dose D-Gal combined with bile duct ligation could establish a stable and high survival animal model of hyperbilirubinemia,which provided a practical and reliable animal model for clinical research.