硫代乙酰胺诱导的急性肝损伤大鼠肝组织Norrin/Frizzled-4表达的变化  

Expression of Norrin/Frizzled-4 in liver tissues of rats with thioacetamide-induced acute liver injury

作　　者：胡建鹏 宋正己[2] 李玉莲[2] 寻琳婷[2] 赵雪茹[2] 张镕 Hu Jianpeng;Song Zhengji;Li Yulian(Medical School,Kunming University of Science and Technology,Kunming 650500,Yunnan Province,China)

机构地区：[1]昆明理工大学医学院,昆明市650500 [2]云南省第一人民医院消化科

出　　处：《实用肝脏病杂志》2018年第2期187-190,共4页Journal of Practical Hepatology

基　　金：国家自然科学基金资助项目(编号:81560107);云南省应用基础研究项目(编号:2014FB091)

摘　　要：目的建立硫代乙酰胺(TAA)诱导的大鼠急性肝损伤模型,探讨Norrin/Frizzled-4在肝损伤间质重建中的作用。方法随机将32只SD大鼠分为正常对照组(N组)8只和TAA诱导组(M组)24只。建立TAA诱导的肝损伤大鼠模型。采用ELISA法检测血清CD105和血管内皮细胞生长因子(VEGF)水平,采用Western blot法检测原代肝星状细胞和肝组织Norrin/Frizzled-4信号通路中细胞外配体蛋白Norrin和细胞膜特异性受体蛋白Frizzled-4的表达。结果 24只TAA诱导组大鼠死亡11只(45.8%);病理学检查显示急性肝损伤大鼠模型建立成功;对照组血清CD105水平为(2.18±0.05)ng/mL,显著低于TAA处理1 w组的(2.36±0.07)ng/mL或2 w组的(2.42±0.03)ng/mL,差异均有显著性(P<0.05);对照组血清VEGF为(61.48±0.39)pg/mL,显著低于模型组的(64.52±0.25)pg/mL,差异均有显著性(P<0.01);原代肝星状细胞和正常肝组织不表达Norrin蛋白或Frizzled-4蛋白,或表达量很低,急性肝损伤大鼠肝组织Norrin/Frizzled-4表达显著高于正常对照组,差异均有显著性(P<0.01)。结论急性肝损伤大鼠肝组织Norrin/Frizzled-4蛋白表达上调,可能与急性肝损伤初期维持血管网络形态及肝间质重建有关。Objective To investigate the roles of Norrin/Frizzled-4 in the interstitial remodeling of acute liver injury.Methods 32 healthy male rats were randomly divided into control(n=8)and model group(n=24).The model of acute liver injury was established by thioacetamide(TAA)injuction.Western blot was used to detect the expression of Norrin/Frizzled-4 protein in liver tissues,and enzyme-linked immunosorbent assay was performed to measure serum CD105 and vascular endothelial growth factor(VEGF)levels.Results There were 11(45.8%)out of 24 rats died in model group during model establishment.Hematoxylin-eosin staining showed that the acute liver injury model was successfully established.Serum CD105 level was(2.18±0.05)ng/mL and VEGF was(61.48±0.39)pg/mL in control group,significantly lower than[(2.36±0.07)ng/mL and[(62.09±0.54)pg/mL,P<0.05]in TAA-treated for one week,or[2.42±0.03)ng/mL and(64.52±0.25)pg/mL,P<0.05]in TAA-treated for two week;Western blot analysis showed that the expressions of Norrin/Frizzled-4 proteins in model group were higher than in normal control group or in primary hepatic stellate cells(P<0.01).Conclusion The expressions of Norrin/Frizzled-4 proteins increase in liver tissues of rats with acute liver injury,which might be related to the maintaing of vascular network morphology and interstitial remodeling.

关 键 词：肝损伤 Norrin/Frizzled-4信号通路 间质重建 硫代乙酰胺 大鼠 

分 类 号：R575[医药卫生—消化系统]