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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 protective effect of ebselen on hepatic encephalopathy (HE) in rats and its mechanism. Methods Wistar rats were randomly divided into 4 groups: blank control group (Ⅰ), HE model group (Ⅱ), ebselen treatment group (Ⅲ) and solvent control group (Ⅳ). Intraperitoneal injection of thioacetamide (TAA), the establishment of stage Ⅱ HE model were given saline, ebselen and dimethyl sulfoxide (DMSO) for 1 week. The contents of 3-NT, ALT, MDA and the activity of superoxide dismutase (SOD) in each group were detected. The pathological changes in the liver were observed. Results The symptoms of HE in group Ⅲ were slower than those in groups Ⅱ and Ⅳ. There were significant differences in serum indexes between group Ⅲ and group Ⅱ and group Ⅳ (P <0.05), but there was no significant difference between group Ⅲ and group Ⅰ P> 0.05). Conclusion Ebselen can protect TA rats from HE-induced HE and slow down the development of HE. The mechanism may be related to ebselen can clear the body of peroxynitrite anion and prevent tyrosine nitration.