乳胞素对SD大鼠脑出血模型神经新生的影响及机制

Effect of lactacystin on nerve newborn ability of intracerebral hemorrhage model and its mechanism

目的探讨UPS抑制剂乳胞素（lactacystin）对SD大鼠脑出血模型神经新生的影响及机制。方法采用Ⅶ型胶原酶诱导SD大鼠脑出血模型,分为对照组（A组）,乳胞素处理组（B组）,每组各20只;造模成功后第1~7天B组腹腔注射1mg/（kg.d）的乳胞素,A组腹腔注射等剂量生理盐水。第3周断头处死SD大鼠,以组织化学方法结合灰度值半定量检测泛素-蛋白酶体系统活性表达,采用分光光度计测定法检测转录因子-核因子-κB（nuclear factor-κB,NF-κB）含量,利用抗Brdu单克隆抗体,显示纹状体区神经前体细胞增殖的能力。结果与A组比较,B组泛素-蛋白酶体系统活性明显下降,损毁侧纹状体内NF-κB含量含量明显减少,神经前体细胞增殖的能力增强（P〈0.01）。结论乳胞素有利于SD大鼠脑出血模型神经新生,其机制可能与抑制泛素-蛋白酶体,调控NF-κB含量,减少神经元凋亡,促进神经元新生有关。

ObjectiveTo investigate the effect of lactacystin on nerve newborn ability of Sprague-Dawley rat intracerebral hemorrhage model and its mechanism.MethodsMale SD rats were divided into control group（group A）,lactacystin group（group B）,and each group of 20 rats.In the first 1～7 days,group B was intraperitoneally injected 1 mg/（kg·d） lactacystin,groups A was intraperitoneally injected equal dose of normal saline.In the third week,all rats were decapitated,UPS and NF-κB content in striatum was measured by using spectrophotometer tyrosine.Brdu-positive neurons in striatum were identified by immunohistochemistry.ResultsCompared with group A,UPS and NF-κB content in striatum of group B decreased significantly（P0.01）,in damaged side of the striatum Brdu-positive cell counts increased（P0.01）.ConclusionNerve newborn ability of Sprague-Dawley rat intracerebral hemorrhage model was promoted by lactacystin,its mechanism may be related to suppress the UPS,regulative NF-κB content,reduce the neuron to apoptosis,and thus promote the neuron newborning.