硫化氢调控Nrf2-HO-1信号通路对休克大鼠肺损伤的保护作用  

Effect of hydrogen sulfide on lung injury in traumatic hemorrhagic shock rats through regulation of Nrf2-HO-1 signaling pathway

作　　者：黄朝露 赵晓勇 林丽丽[1] 徐文莉 李海燕[3] HUANG Chaolu;ZHAO Xiaoyong;LIN Lili;XU Wenli;LI Haiyan(First Clinical Medical College,Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学第一临床医学院,325000 [2]潍坊医学院附属医院麻醉科 [3]温州医科大学附属第一医院康复科

出　　处：《浙江医学》2021年第11期1155-1159,共5页Zhejiang Medical Journal

基　　金：国家自然科学基金资助项目(81501954);山东省医药卫生科技发展计划项目(2019WS605)。

摘　　要：目的通过观测外源性硫化氢(H_(2)S)硫氢化钠(NaHS)对核转录因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路的作用,探讨H_(2)S对创伤失血性休克所致肺损伤的保护作用。方法健康清洁级雄性SD大鼠36只,随机分成NaHS处理组(NaHS组)、模型组(HTS组)、假手术组(Sham组),每组12只。HTS组、NaHS组大鼠作腹部切口并放血建立创伤失血性休克模型,然后用林格液复苏[NaHS组复苏前腹腔注射0.5 ml NaHS(28μmol/kg),HTS组予等量0.9%氯化钠注射液];Sham组仅作腹部切口,不放血、不复苏。2 h后检测血清中H_(2)S浓度及超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)水平,计算肺系数、肺湿/干重比,HE染色评价肺组织病理变化。Western blot法检测大鼠肺组织Nrf2和HO-1蛋白表达水平。结果与Sham组比较,HTS组H_(2)S浓度及SOD、MDA、MPO水平差异均有统计学意义(均P<0.05);与HTS组比较,NaHS组H_(2)S浓度及SOD、MDA、MPO水平差异均有统计学意义(均P<0.01)。与Sham组比较,HTS组肺系数、肺湿/干重比均明显增加(均P<0.05);相对于HTS组,NaHS组肺系数、肺湿/干重比均显著下降(均P<0.01)。HE染色结果显示Sham组肺泡形态结构基本完整,轮廓清晰,未见病变;HTS组肺泡壁明显增厚,出现水肿和炎性细胞浸润;而NaHS组大鼠肺泡水肿和炎性浸润情况明显改善。与Sham组比较,HTS、NaHS组Nrf2、HO-1蛋白表达水平均明显升高(均P<0.05);与HTS组比较,NaHS组Nrf2、HO-1蛋白表达水平均明显升高(均P<0.01)。结论外源性H_(2)S通过调控Nrf2-HO-1信号通路对创伤失血性休克大鼠肺损伤产生保护作用。Objective To investigate the protective effect of exogenous hydrogen sulfide(H_(2)S)on traumatic hemorrhagic shock-induced lung injury of rats and its mechanism.Methods Thirty-six male SD rats were randomly divided into sodium hydrosulfide hydrate treatment group(NaHS group),model group(HTS group),and sham operation group(Sham group)with 12 rats in each group.The traumatic hemorrhagic shock model was prepared with abdominal incision,and resuscitated with Linger solution after bloodletting.Before resuscitation,the NaHS group was given intraperitoneal injection of 0.5 ml NaHS(28μmol/kg),and the HTS group was given the same amount of 0.9%sodium chloride.Abdominal incision operation was given to rats in sham group,but no bloodletting and resuscitation.After 2 hours the serum H_(2)S,superoxide dismutase(SOD),malondialdehyde(MDA),and myeloperoxidase(MPO)levels were detected,the lung coefficient and lung wet/dry weight were calculated.The lung tissue pathological changes was observed by HE staining.Western blotting was used to detect the expression of nuclear transcription factor E2-related factor2(Nrf2)and heme oxygenase(HO-1)in rat lung tissue.Results Compared with the Sham group,the H_(2)S concentration and SOD,MDA,MPO levels in the HTS group were significantly different(all P<0.05),compared with the HTS group,the NaHS group H_(2)S concentration and the SOD,MDA,and MPO levels were significantly different(all P<0.01).Compared with the Sham group,the lung coefficient and lung wet/dry weight ratio in the HTS group increased significantly(all P<0.05),compared with the HTS group,the lung coefficient and lung wet/dry weight ratio in the NaHS group de-creased significantly(all P<0.01).Histopathological examination showed that the alveolar wall was significantly thickened,with obvious edema and inflammatory cell infiltration,while in the NaHS group,the alveolar edema and inflammatory infiltra-tion were significantly ameliorated.Compared with the Sham group,the protein expression levels of Nrf2 and HO-1 in the HTS and NaHS g

关 键 词：休克性肺损伤 硫化氢 核转录因子 E2相关因子2 氧化应激 

分 类 号：R605.971[医药卫生—急诊医学]