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山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (5): 154-.

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依布硒啉对肝性脑病大鼠的保护作用

荣琳1,邵丽华1,郗德凤1,王淑娥1,王希峰1,汪心婷2,马立宪3   

  1. 山东大学 1.公共卫生学院卫生检验研究所, 济南 250012;2. 公共卫生学院流行病与卫生统计学研究所,
     济南 250012;3.齐鲁医院感染病科,济南 250012
  • 收稿日期:2010-03-08 出版日期:2010-05-16 发布日期:2010-05-16
  • 通讯作者: 邵丽华,教授,主要从事色谱分析在卫生检验中的应用研究。 E-mail:slh@sdu.edu.cn
  • 作者简介:荣琳(1981- ),女,硕士研究生,主要从事色谱分析在卫生检验中的应用研究。
  • 基金资助:

    山东省自然科学基金资助课题(Y2007C079)。

Inhibitory effects of ebselen on hepatic encephalopathy of rats

RONG  Lin1, SHAO  Lihua1,CHI  Defeng1, WANG  Shue1, WANG  Xifeng1, WANG  Xinting2, MA  Lixian3   

  1. 1. Institute of Chemistry and Microbacteria Detection, School of Public Health, Shandong University, Jinan 250012, China;
    2. Institute of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan 250012, China;
     3. Department of Infectious Diseases, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2010-03-08 Online:2010-05-16 Published:2010-05-16

摘要:

目的  探讨依布硒啉对肝性脑病(HE)大鼠的保护作用并探讨其机制。方法  Wistar大鼠随机分为4组:空白对照组(Ⅰ),HE模型组(Ⅱ),依布硒啉处理组(Ⅲ)和溶剂对照组(Ⅳ)。用硫代乙酰胺(TAA)腹腔注射,建立Ⅱ期HE模型后分别给予生理盐水、依布硒啉和二甲基亚砜(DMSO)灌胃1周。检测各组血清3-硝基酪氨酸(3NT)、谷丙转氨酶(ALT)、丙二醛(MDA)的含量及超氧化物歧化酶(SOD)的活性;观察肝脏的病理改变。结果  Ⅲ组大鼠HE症状较Ⅱ组和Ⅳ组进展缓慢;Ⅲ组与Ⅱ组、Ⅳ组比较各血清指标差异均有统计学意义(P<0.05),与Ⅰ组比较差异无统计学意义(P>0.05)。结论  依布硒啉对TAA诱导的HE大鼠有一定的保护作用,可减缓HE的发展。其机制可能与依布硒啉能够清除体内过氧亚硝酸阴离子且阻止酪氨酸硝基化有关

关键词: 依布硒啉;肝性脑病;3硝基酪氨酸

Abstract:

Objective  To investigate the inhibitory role of ebselen on hepatic encephalopathy (HE) of rats and explore the probable mechanism. Methods  40 male Wistar rats were divided into 4 groups randomly: blank control group (Ⅰ), HE model group (Ⅱ), ebselen treated group (Ⅲ) and solvent control group (Ⅳ). All the groups were treated with thioacetamide (TAA) by intraper-itoneal injection except group Ⅰ (treated with normal saline) to manufacture the model of HE. Then the 4 groups were intragastrically administered with normal saline (Ⅰ, Ⅱ), ebselen (Ⅲ) and dimethyl sulfoxide (DMSO) (Ⅳ) respectively for 1 week untill the symptoms of HE changed. The rats were sacrificed to collect blood for the following detection of 3-nitrotyrosine, alanine transarninase, malondialdehyde and superoxide dismutase. Pathological sections were made to observe the liver changes. Results  The development of HE was slower in group Ⅲ  than in groups Ⅱ and Ⅳ; and the differences of serum markers between groups Ⅲ and Ⅱ, and between groups Ⅲ and Ⅳ were significant (P<0.05), while the difference between groups Ⅲ andⅠwere not obvious (P>0.05). Conclusions  The results suggest that ebselen probably has inhibitory effect on HE of rats induced by TAA and can delay the development of HE. The mechanism may be related to the capability of ebselen, which can clear peroxynitrite anion and inhibit the nitration of tyrosine.

Key words: Ebselen; Hepatic encephalopathy; 3-nitrotyrosine 

中图分类号: 

  • R575.3
[1] 范桂玲1,姚勇2,姚丽3,贾崇奇4. 乙醇脱氢酶2基因的Arg47His变异与慢性乙型肝炎的关系[J]. 山东大学学报(医学版), 2011, 49(11): 101-104.
[2] 叶青1,荣琳2,汪心婷3,邵丽华2. 肝性脑病大鼠肝及脑组织蛋白质硝基化和细胞凋亡的研究[J]. 山东大学学报(医学版), 2010, 48(8): 38-41.
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