硫代乙酰胺诱导大鼠持久性肝纤维化模型的制备  

Establishment of a rat model of thioacetamide induced hepatic fibrosis

作　　者：薛改[1,2] 刘建芳[1] 闫成[1] 张庆霞[1] 郑丽[1] 侯艳宁[1,2] 

机构地区：[1]白求恩国际和平医院药剂科,河北省石家庄市050082 [2]河北医科大学研究生学院,河北省石家庄市050017

出　　处：《世界华人消化杂志》2015年第12期1937-1942,共6页World Chinese Journal of Digestology

基　　金：军队"十二五"重点课题基金资助项目;No.BWS11J002~~

摘　　要：目的:用硫代乙酰胺(thioacetamide,TAA)灌胃法诱导大鼠形成肝纤维化,建立一种稳定持久实用的大鼠肝纤维化模型.方法:将♂SD大鼠随机分为正常组和模型组,模型组采用质量浓度为3%的TAA对SD大鼠进行隔天灌胃,灌胃量为160 mg/kg体质量[灌胃体积(m L)为体质量(g)/187.5];正常组采用溶剂蒸馏水代替TAA灌胃.灌胃6 w k后处死大鼠,采集血清和肝组织,血清分别进行肝功能(血氨、碱性磷酸酶、总胆红素、白蛋白/球蛋白)和细胞因子[肝细胞生长因子(hepatocyte growth factor,HGF)、肝素结合表皮生长因子(heparin-binding epidermal growth factor,HB-EGF)、白介素-6(interleukin-6,IL-6)、a-平滑肌抗体(a-smooth muscle antibody,a-SMA)]水平检测,肝组织分别进行HE和Masson染色,并对纤维化程度进行病理分级.留取部分成模大鼠,停止灌服TAA 11 wk后,取肝组织做HE染色,观察肝纤维化自愈情况.结果:TAA灌胃6 wk后,大鼠肝纤维化形成率为100%.与对照组相比,模型组大鼠肝功能变化显著,其中血氨、碱性磷酸酶和总胆红素浓度显著升高,白蛋白/球蛋白比值显著降低(P<0.01);血清中细胞因子HGF与HBEGF水平显著降低,IL-6、a-SMA水平显著升高(P<0.01).停用TAA 11 wk后,与11 wk前相比,HE染色显示肝组织纤维化程度,未见显著变化.结论:TAA灌胃6 wk可以形成稳定和持久的肝纤维化,肝纤维化形成率高且速度快,是一种简便实用的肝纤维化模型制备方法.AIM： To establish a stable and efficient rat model of thioacetamide （TAA） induced hepatic fibrosis.METHODS： Male SD rats were randomly divided into a normal group and a model group. The model group was intragastrically administrated 3% TAA at 160 mg/kg body weight and the normal group was administrated distilled water. Serum and hepatic tissue samples were collected after 6 wk. Serum levels of ammonia （BAM）, alkaline phosphatase （AKP）, total bilirubin （TBIL）, albumin/globulin （ALB/GLB） and cell factors including hepatocyte growth factor （HGF）, heparin- binding epidermal growth factor （HB- EGF）, interleukin-6 （IL-6）, and （x-smooth muscle antibody （（x-SMA） were detected. Histopathological examination of liver tissue was conducted by HE staining and Masson staining, and the degree of liver fibrosis was observed under a microscope. The natural repair of hepatic fibrosis was observed by HE staining 11 wk after stopping administration of TAA. RESULTS： The rate of hepatic fibrosis was 100% after intragastric administration of TAA for 6 wk. Compared with the control group, the liver function in the model group changed significantly; serum levels of BAM, AKP and TBIL increased significantly, and the ratio of ALB/GLB decreased significantly （P 〈 0.01）. Serum levels of HGF and HB-EGF decreased significantly, and serum IL-6 and a-SMA increased significantly （P 〈 0.01）. The degree of hepatic fibrosis was not changed until 11 weeks after stopping TAA. CONCLUSION： A stable and persistent rat model of hepatic fibrosis has been successfully prepared by intragastric administration of TAA for 6 wk. This is a convenient and practical method to establish a rat liver fibrosis model with a high rate of hepatic fibrosis formation.

关 键 词：肝纤维化 肝硬化 硫代乙酰胺 灌胃法 

分 类 号：R575.2[医药卫生—消化系统] R-332[医药卫生—内科学]