免疫性食蟹猴肝纤维化模型的实验研究

目的：在食蟹猴上，通过皮下注射异种血清的方法建立免疫性肝纤维化模型，阐明该模型的特点。方法：选择雄性食蟹猴12例，随机分为模型组和对照组。模型组皮下注射小牛血清，剂量为0.4 ml/kg；对照组注射相同剂量的生理盐水。每周均注射两次。结果：造模第8周开始，模型组血清HA、PCⅢ、ⅣC、TGF-β1和α-SMA均较造模前显著升高（P<0.05，P<0.01），模型组HA和PCⅢ比对照组显著升高（P<0.05）。造模第12周后，模型组血清ⅣC、TGF-β1和α-SMA均比对照组显著升高（P<0.05），模型组血清LN和TCH水平较造模前显著升高（P<0.05）；模型组血清AST和ALT水平比对照组以及造模前均显著升高（P<0.05）,模型组ALB比造模前显著下降（P<0.05）。造模16周，模型组血清LN、TCH和TG水平比对照组显著升高（P<0.05）；模型组ALB水平明显低于对照组（P<0.05）；B超显示模型组肝脏光点较对照组粗糙，显示强光回声团；HE染色下显示，模型组肝细胞坏死和单核细胞浸润；Van-Gieson胶原染色下显示，模型组肝脏汇管区胶原纤维增生。结论：给予皮下注射小牛血清16周，成功建立食蟹猴肝纤维化模型。

Establishment of immune liver fibrosis models in cynomolgus monkeys

Objective:To establish liver fibrosis models in cynomolgus monkey using calf serum. Methods: Healthy cynomolgus monkeys were randomly divided into control group and model group,and there were 6 animals in each group.Model group were treated with calf serum subcutaneously at the dose of 0.4 ml/kg,and control group were received the same dose of normal saline.Calf serum will be administrated twice a week. Results: After 8 weeks of administration,the serum HA,PCⅢ,ⅣC,TGF-β1 and α-SMA in model group were increased differently when compared with modeling before（P<0.05，P<0.01）,and the serum HA and PCⅢ in model group were also increased significantly when compared with control group.After 12 weeks of administration,the serum ⅣC,TGF-β1 and α-SMA in model group were increased significantly compared with control group（P<0.05）,and the serum LN and TCH in model group were increased obviously when compared with modeling before（P<0.05）,the levels of serum AST and ALT in model group were also increased distinctly as compared with control group and modeling before（P<0.05）,while the serum ALB in model group was decreased significantly when compared with modeling before（P<0.05）.At week 16,the serum LN,TCH and TG in model group were increased significantly when compared with control group（P<0.05）;while the serum ALB in model group was decreased distinctly when compared with control group（P<0.05）；the strong echo were showed in liver of model group by using ultrasonography;pathological examination showed that there were necrosis and monocyte infiltrating in liver of model group,and collagen fiber proliferation were observed in portal area of model group.Conclusion: Liver fibrosis models can be established successfully in cynomolgus monkeys by subcutaneously injecting calf serum for 16 weeks.