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山东大学学报(医学版) ›› 2011, Vol. 49 ›› Issue (8): 52-56.

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酒精性肝病中蛋白酶体活性抑制与内质网应激相关性的体外实验

关慧,刘慧敏,贾晓青,罗争,阎明   

  1. 山东大学齐鲁医院消化内科, 济南 250012
  • 收稿日期:2011-03-11 出版日期:2011-08-10 发布日期:2011-08-10
  • 通讯作者: 阎明(1956- ),男,博士,主任医师,教授,主要从事酒精性肝病发病机制的研究。 E-mail:ymylh@163.com
  • 作者简介:关慧(1984- ),女,硕士研究生,主要从事酒精性肝病发病机制的研究。 E-mail:karenguan2008@163.com

In vitro study of the correlation between inhibited ubiquitin proteasome  activity and endoplasmic reticulum stress in alcoholic liver disease

GUAN Hui, LIU Huimin, JIA Xiaoqing, LUO Zheng, YAN Ming   

  1. Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2011-03-11 Online:2011-08-10 Published:2011-08-10

摘要:

目的探讨酒精性肝病中蛋白酶体活性的抑制与内质网应激间的相关性。方法      乙醇处理HepG2细胞建立酒精性肝损伤体外模型。设立对照组、乙醇处理组、蛋白酶体活化剂桦木酸处理组及桦木酸加乙醇共同处理组,测定各组内质网应激标志物葡萄糖调节蛋白78(glucose regulation protein 78,GRP78)基因表达水平的变化,同时测定蛋白酶体活性和细胞内甘油三酯含量。结果     乙醇处理组蛋白酶体活性降低,GRP78表达增高,细胞内甘油三酯含量增多;而桦木酸组结果相反;蛋白酶体活性变化与GRP78表达水平呈负相关,GRP78表达水平与甘油三酯含量呈正相关。结论     乙醇处理可通过抑制蛋白酶体活性诱发内质网应激;桦木酸可提高蛋白酶体活性而降低内质网应激严重程度;蛋白酶体活性变化与内质网应激严重程度呈负相关性,后者可加剧酒精性肝损伤。

关键词: 肝病,酒精性;内质网应激;泛素蛋白酶体

Abstract:

Objective      To study the potential correlation between inhibited proteasome activity and occurrence and development of endoplasmic reticulum stress(ERS) in alcoholic liver disease(ALD). Methods      HepG2 cells were treated  with  ethanol to establish an in vitro model of ALD, and then treated with betulinic acid or with both ethanol and betulinic acid. The mRNA expression of glucose regulation protein 78 (GRP78), a ERS marker, was detected. Also, proteasome activity and intracellular triglyceride(TG) content in different groups were detected. Results      Ethanol inhibited activity of proteasome, with increases of GRP78 mRNA expression and intracellular TG content. Betulinic acid promoted the proteasome activity with reductions of GRP78 mRNA level and TG content. Correlation analysis revealed a negative relativity between proteasome activity and expression of GRP78 mRNA. While the GRP78 mRNA level and intracellular TG content had a positive relativity. Conclusion      Ethanol can inhibit proteasome activity, thus inducing ERS, while betulinic acid can promote proteasome activity, thus reducing ERS. The proteasome activity and ERS have some negative relativity, and the latter aggravates pathogenesis of ALD.

Key words: Liver disease, alcoholic; Endoplasimic reticulum stress; Ubiquitin proteasome

中图分类号: 

  • R575.5
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