实用肝脏病杂志 ›› 2018, Vol. 21 ›› Issue (2): 187-190.doi: 10.3969/j.issn.1672-5069.2018.02.008

• 实验性肝炎 • 上一篇    下一篇

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*

胡建鹏, 宋正己, 李玉莲, 寻琳婷, 赵雪茹, 张镕   

  1. 650500 昆明市 昆明理工大学医学院(胡建鹏,张镕); 云南省第一人民医院消化科(宋正己,李玉莲,寻琳婷,赵雪茹)
  • 收稿日期:2017-03-30 出版日期:2018-03-10 发布日期:2018-03-19
  • 通讯作者: 宋正己,E-mail: song4715@163.com
  • 作者简介:胡建鹏,女,25岁,硕士研究生。主要从事慢性肝病细胞分子生物学研究。E-mail:hujianpeng2013_sl@126.com
  • 基金资助:
    *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)

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

Hu Jianpeng, Song Zhengji, Li Yulian, et al   

  1. Medical School,Kunming University of Science and Technology,Kunming 650500,Yunnan Province,China
  • Received:2017-03-30 Online:2018-03-10 Published:2018-03-19

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。

关键词: 肝损伤, Norrin/Frizzled-4信号通路, 间质重建, 硫代乙酰胺, 大鼠

Abstract: 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.

Key words: Acute liver injury, Norrin/Frizzled-4 signaling pathway, Interstitial reconstruction, Thioacetamide, Rats