大鼠慢加急性肝功能衰竭模型的制备

目的：探索建立大鼠慢加急性肝功能衰竭模型的方法。方法SD 大鼠40只，随机分为正常对照组、模型1组、模型2组和模型3组，每组各10只。模型1组：每周二、五腹膜内注射40％ CCl41 mL/kg；持续4周；模型2组：每周二、五腹膜内注射40％ CCl41 mL/kg，每周三腹膜内注射猪血清0．5 mL，持续4周；模型3组：每周二、五腹膜内注射40％CCl40．7 mL/kg，每周三腹膜内注射猪血清0．3 mL，持续4周，以5％乙醇代水，自由饮用；正常对照组：不注射任何药物。实验第29天，各模型组大鼠均腹膜内注射脂多糖（LPS）30μg/kg＋犇-氨基半乳糖（犇-Gal ）0．3 g/kg。以全自动生化分析仪检测大鼠血清 ALT、AST 和 TBil 水平。肝组织切片 HE 染色后光学显微镜镜下观察病理学变化。结果造模4周后各模型组大鼠血清 ALT、AST 和 TBil 水平均明显高于正常对照组（均P＜0．01），以模型3组最高、模型2组其次，3组间差异均有统计学意义（均P＜0．01）。注射 LPS＋犇-Gal 后24 h，模型3组中有3只动物死亡，3个模型组大鼠的 ALT、AST和 TBil 水平均较注射前明显升高（均P＜0．01），3组间差异均有统计学意义（均P＜0．01）。注射 LPS＋犇-Gal 后72 h，各模型组大鼠 ALT、AST 和 TBil 水平均较前明显降低（均P＜0．01），但仍明显高于正常对照组（均P＜0．01），3组间差异仍均有统计学意义（均P＜0．01）。注射 LPS＋犇-Gal 后24 h，肝窦明显扩张、充血，大量炎性细胞浸润于汇管区，小叶内见肝细胞坏死。结论采用40％ CCl4＋猪血清诱导慢性肝损伤后，再以 LPS 30μg/kg＋犇-Gal 0．3 g/kg 攻击，可成功制备大鼠慢加急性肝功能衰竭模型。

An approach for building a model of acute on chronic liver failure in rat

Objective To explore an approach for building a model of acute on chronic liver failure （ACLF）in rat.Methods Forty SD rats were randomly divided into normal control group,model group 1 ,model group 2 and model group 3,10 rats for each group.Intraperitoneal injection （ip）for 40% carbon tetrachloride （CCl4 ）1 mL＆#183;kg-1 was performed for rats in group 1 ,2 and 3 at the 2nd and 5th days every week totally for 4 weeks,respectively.Additional ip for porcine serum 0.5 mL or 0.3 mL was performed for rats in group 2 or 3 at the 3rd day every week totally for 4 weeks,respectively. All rats in model groups drank 5% ethanol freely instead of water.Not any drug injection was performed for rats in normal control group.At the 29th day,lipopolysaccharide （LPS）30 μg＆#183;kg-1 plus D-galactosamine （D-Gal）0.3 g＆#183;kg-1 ip were performed in all rats.Serum alanine aminotransferase （ALT）,aspartate aminotransferase （AST）and total bilirubin （TBI） level were detected by the automatic biochemical analyzer.Preparation of liver tissue sections,HE staining and pathological changes were observed by microscope.Results （1）After 4 weeks drug administration,serum ALT,AST and TBil levels of rats in group 1 ,2 and 3 were significantly higher than those in control group （P＆lt;0.01）,difference among 3 groups was statistically significant （P＆lt;0.01）.（2）Three rats in group 3 died 24 hours after the injection of LPS plus D-Gal.Serum ALT,AST and TBil levels in group 1 ,2 and 3 were significantly increased compared to before injection （P＆lt;0.01 ）,and there was statistically significant difference between any two groups （P＆lt;0.01）.（3）Serum ALT,AST and TBIL levels in group 1 ,2 and 3 decreased 72 hours after injection of LPS plus D-Gal,however,the decreased value was still significantly higher than that of control group （P＆lt;0.01 ）.（4）It was observed that hepatic sinusoidal dilatation,hyperemia,inflam-matory cell infiltration in the portal area,necrosis of hepatocytes in hepatic lobule intact fibrosis septa.Conclusion An ani-mal model of ACLF was built by treating rats with 40% CCl4 plus pig serum albumin and later with LPS of 30 μg＆#183;kg-1 plus D-Gal 0.3 g＆#183;kg-1 ,which is a potential and novel model for the study of ACLF.