免疫性食蟹猴肝纤维化模型的实验研究

摘要

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.%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,PC Ⅲ,Ⅳ C,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 PC Ⅲ in model group were also increased significantly when compared with control group.After 12 weeks of administration,the serum Ⅳ C,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.