依布硒啉对肝性脑病大鼠的保护作用  

Inhibitory effects of ebselen on hepatic encephalopathy of rats

作　　者：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] 

机构地区：[1]山东大学公共卫生学院卫生检验研究所,济南250012 [2]山东大学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

出　　处：《山东大学学报（医学版）》2010年第5期154-156,160,共4页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金资助课题(Y2007C079)

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。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 randomly divided into 4 groups ： the blank control group （ Ⅰ ）, the HE model group （ Ⅱ ）, the ebselen treated group （ Ⅲ ） and the solvent control group （ Ⅳ ）. All the groups were treated with thioacetamide （TAA） by intraperitoneal injection except group I （treated with normal saline） to manufacture the model of HE. Then the 4 groups were intragastricaUy administered with normal saline （ I , Ⅱ ）, eb- selen （ Ⅲ ） and dimethyl sulfoxide （DMSO） （Ⅳ） for 1 week until the symptoms of HE changed. The rats were sacri- ficed to collect blood for detection of 3-nitrotyrosine, alanine transarninase, malondialdehyde and superoxide dismutase. Pathological sections were made to observe 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 and I were not obvious （ P 〉 0.05 ）. Conclu- sions The results suggest that ebselen probably has an 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 ani- ons and inhibit the nitration of tyrosine.

关 键 词：依布硒啉 肝性脑病 3-硝基酪氨酸 

分 类 号：R575.3[医药卫生—消化系统]