呋塞米对脑出血模型大鼠PERK/eIF2α/CHOP通路及继发性脑损伤的影响  

Effects of furosemide on PERK/eIF2α/CHOP pathway and secondary brain injury in rat models with intracerebral hemorrhage

作　　者：张瑜[1] 高建洲[1] 韩韶 ZHANG Yu;GAO Jian-zhou;HAN Shao(Department of Neurosurgery, East Campus, Handan First Hospital, Handan 056000, China)

机构地区：[1]邯郸市第一医院东院区神经外科,河北邯郸056000

出　　处：《基础医学与临床》2022年第1期100-105,共6页Basic and Clinical Medicine

基　　金：河北省2020年度医学科学研究计划(20200185)。

摘　　要：目的探讨呋塞米(FUR)对脑出血(ICH)大鼠RNA依赖的蛋白激酶样内质网激酶(PERK)/真核起始因子2α(eIF2α)/转录因子CCAAT增强子结合蛋白的同源蛋白(CHOP)通路及继发性脑损伤的影响。方法将大鼠分为假手术组、模型组(脑定位注射Ⅳ型胶原酶,建立ICH模型)、FUR低剂量组(FUR-L)、FUR中剂量组(FUR-M)、FUR高剂量组(FUR-H)、神经节苷脂组,每组18只。药物处理后,检测神经功能,对其进行Longa评分;测量大脑含水量;用Evans蓝外渗实验检测血脑屏障损伤;用HE染色检测海马神经元损伤;用酶联免疫吸附法(ELISA)检测血清γ干扰素(IFN-γ)、白细胞介素-6(IL-6)水平;用免疫印迹法检测大鼠脑组织PERK/eIF2α/CHOP通路相关蛋白p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达。结果相比假手术组,模型组大鼠海马神经元变性坏死,皱缩变小,数目明显减少,呈现严重病理损伤,Longa评分、Evans蓝渗出量、大脑含水量、血清IFN-γ及IL-6水平、p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达水平明显升高(P<0.05)。相比模型组,FUR-L、FUR-M、FUR-H组及神经节苷脂组大鼠海马神经元形态有不同程度恢复,病理损伤减轻,Longa评分、大脑含水量、Evans蓝渗出量、血清IFN-γ及IL-6水平、p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达水平均降低(P<0.05)。结论FUR可下调PERK/eIF2α/CHOP通路蛋白表达,缓解脑水肿及海马神经元损伤,修复ICH模型大鼠神经功能。Objective To investigate the effects of furosemide(FUR)on PERK/eIF2α/CHOP pathway and secondary brain injury in rats with intracerebral hemorrhage(ICH).Methods The rats were divided into sham operation group,model group(intracerebral injection of collagenase typeⅣin ICH),furosemide low dose(FUR-L)groups,medium dose(FUR-M)groups,high dose(FUR-H)groups and ganglioside group,with eighteen rats in each.After treatment,the neurological function was evaluated and scored by Longa and the water content of brain tissue was measured;Evans blue extravasation test was used to detect the blood-brain barrier injury;HE staining microscopy was used to detect the damage of hippocampus neurons;enzyme-linked immunosorbent assay(ELISA)was used to detect the serum level of interferon-γ(IFN-γ)and interleukin-6(IL-6);Western blot was used to detect the expression of p-PERK/PERK,p-eIF2α/eIF2αand CHOP.Results Compared with those in the sham operation group,the hippocampal neurons in the model group were degenerated and necrotic,the shrinkage was smaller,the number was significantly decreased,severe pathological damage was found,Longa score,Evans blue exudation,brain water content,level of serum IFN-γand IL-6,the expression of p-PERK/PERK,p-eIF2α/eIF2αand CHOP were all significantly increased(P<0.05).Compared with those in the model group,The morphological changes of hippocampal neurons in the FUR-L,FUR-M and FUR-H groups and ganglioside group were restored to different degrees and the pathological damage was alleviated,Longa score,brain water content,Evans blue exudation,level of serum IFN-γand IL-6,expression of p-PERK/PERK,p-eIF2α/eIF2αand CHOP were decreased(P<0.05).Conclusions Furosemide can down-regulate the expression of PERK/eIF2α/CHOP pathway protein,relieve brain edema and hippocampal neuron damage and repair the neural function in ICH animal.model.

关 键 词：呋塞米 脑出血 PERK/eIF2α/CHOP通路 脑损伤 

分 类 号：R743.34[医药卫生—神经病学与精神病学]