硫化氢急性中毒大鼠肺组织氧化应激和Nrf2基因表达及乌司他丁的影响
류화경급성중독대서폐조직양화응격화Nrf2기인표체급오사타정적영향
Effect of ulinastatin on oxidative stress and nuclear factor E2-related factor 2 expression in the lung tissues of acute hydrogen sulfide intoxicated rats
  • 万方数据
    中华劳动卫生职业病杂志 중화노동위생직업병잡지
    CHINESE JOURNAL OF INDUSTRIAL HYGIENE AND OCCUPATIONAL DISEASES
    2012年 1期 27-32 ,共6页

    葛赟%孙耒%吴宗盛%姜小珍%邱俏檬%洪广亮%梁欢%李萌芳%卢中秋

    갈빈%손뢰%오종성%강소진%구초몽%홍엄량%량환%리맹방%로중추

    硫化氢%转录因子%急性肺损伤%乌司他丁 硫化氫%轉錄因子%急性肺損傷%烏司他丁
    류화경%전록인자%급성폐손상%오사타정
    Hydrogen sulfide%Transcription factors%Acute lung injury%Ulinastratin
    目的 研究硫化氢急性中毒大鼠肺组织氧化应激水平及核转录因子NF-E2相关因子2(nuclear factor E2-related factor 2,Nrf2)基因表达的变化及乌司他丁(ulinastatin,UTI)的影响.方法 将96只清洁级SD大鼠随机分为正常对照组(8只)、UTI对照组(8只)、硫化氢染毒组(40只)、UTI干预组(40只).正常对照组和UTI对照组大鼠于染毒柜内吸人与硫化氢同样流量的空气1h,UTI对照组大鼠立即腹腔注射UTI(10万U/kg),2h后处死.硫化氢染毒组和UTI干预组大鼠在染毒柜内吸入硫化氢(浓度为283.515 mg/m3)1h,UTI干预组大鼠立即腹腔注射UTI(10万U/kg),两组大鼠分别于2、6、12、24、48 h处死,每组8只.检测肺组织中丙二醛(MDA)含量及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化氢酶(GSH-Px)活力和谷胱甘肽(GSH)含量及Nrf2 mRNA的表达,观察肺组织病理学改变并行肺损伤评分.结果 与正常对照组比较,2、6、12 h硫化氢染毒组大鼠肺组织中SOD、CAT活力和GSH含量及2、6、12、24h GSH-Px活力明显降低,差异有统计学意义(P＜0.01或P＜0.05)；2、6、12、24h硫化氢染毒组大鼠肺组织中MDA含量明显升高,差异有统计学意义(P＜0.01).与相应时间点硫化氢染毒组比较,UTI干预组6、12h时GSH-Px活力,2、6、12h时CAT活力,2、6、12、24h时GSH含量及2、6、12、24、48 h时SOD活力明显升高,差异均有统计学意义(P＜0.01或P＜0.05)；UTI干预组2、6、12h时MDA含量明显低于相应时间点硫化氧染毒组,差异有统计学意义(P＜0.01).染毒后2、6、12、24 h,硫化氢染毒组肺组织中Nrf2 mRNA表达(0.314±0.011、0.269±0.010、0.246±0.011、0.221士0.018)明显高于正常对照组(0.149±0.012),差异有统计学意义(P＜0.01)；与相应时间点硫化氢染毒组比较,2、6、12、24、48 h UTI干预组的Nrf2 mRNA表达(0.383:±-0.017、0.377±-0.014、0.425±0.017、0.407±0.011、0.381±0.010)明显升高,差异均有统计学意义(P＜0.01).光学显微镜下观察可见,硫化氢染毒组染毒后24h大鼠肺组织损害明显,UTI干预组大鼠肺损伤较硫化氢染毒组有所减轻.UTI干预组12、24、48 h时肺损伤评分明显低于相应时间点硫化氢染毒组,差异有统计学意义(P＜0.01).结论 氧化应激和Nrf2活化是参与硫化氢中毒急性肺损伤的重要因素,UTI能抑制氧自由基产生,纠正氧化还原失衡,上调Nrf2 mRNA表达水平,减轻氧化应激损伤,对肺组织损伤有保护作用.
    목적 연구류화경급성중독대서폐조직양화응격수평급핵전록인자NF-E2상관인자2(nuclear factor E2-related factor 2,Nrf2)기인표체적변화급오사타정(ulinastatin,UTI)적영향.방법 장96지청길급SD대서수궤분위정상대조조(8지)、UTI대조조(8지)、류화경염독조(40지)、UTI간예조(40지).정상대조조화UTI대조조대서우염독거내흡인여류화경동양류량적공기1h,UTI대조조대서립즉복강주사UTI(10만U/kg),2h후처사.류화경염독조화UTI간예조대서재염독거내흡입류화경(농도위283.515 mg/m3)1h,UTI간예조대서립즉복강주사UTI(10만U/kg),량조대서분별우2、6、12、24、48 h처사,매조8지.검측폐조직중병이철(MDA)함량급초양화물기화매(SOD)、과양화경매(CAT)、곡광감태과양화경매(GSH-Px)활력화곡광감태(GSH)함량급Nrf2 mRNA적표체,관찰폐조직병이학개변병행폐손상평분.결과 여정상대조조비교,2、6、12 h류화경염독조대서폐조직중SOD、CAT활력화GSH함량급2、6、12、24h GSH-Px활력명현강저,차이유통계학의의(P＜0.01혹P＜0.05)；2、6、12、24h류화경염독조대서폐조직중MDA함량명현승고,차이유통계학의의(P＜0.01).여상응시간점류화경염독조비교,UTI간예조6、12h시GSH-Px활력,2、6、12h시CAT활력,2、6、12、24h시GSH함량급2、6、12、24、48 h시SOD활력명현승고,차이균유통계학의의(P＜0.01혹P＜0.05)；UTI간예조2、6、12h시MDA함량명현저우상응시간점류화양염독조,차이유통계학의의(P＜0.01).염독후2、6、12、24 h,류화경염독조폐조직중Nrf2 mRNA표체(0.314±0.011、0.269±0.010、0.246±0.011、0.221사0.018)명현고우정상대조조(0.149±0.012),차이유통계학의의(P＜0.01)；여상응시간점류화경염독조비교,2、6、12、24、48 h UTI간예조적Nrf2 mRNA표체(0.383:±-0.017、0.377±-0.014、0.425±0.017、0.407±0.011、0.381±0.010)명현승고,차이균유통계학의의(P＜0.01).광학현미경하관찰가견,류화경염독조염독후24h대서폐조직손해명현,UTI간예조대서폐손상교류화경염독조유소감경.UTI간예조12、24、48 h시폐손상평분명현저우상응시간점류화경염독조,차이유통계학의의(P＜0.01).결론 양화응격화Nrf2활화시삼여류화경중독급성폐손상적중요인소,UTI능억제양자유기산생,규정양화환원실형,상조Nrf2 mRNA표체수평,감경양화응격손상,대폐조직손상유보호작용.
    Objective To investigate the dynamic changes of oxidative stress and nuclear factor-E2related factor 2(Nrf2)expression in the lung tissues of acute hydrogen sulfide(H22S)intoxicated rats and intervention effects of ulinastratin(UTI).Methods A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group(n=8),UTI control group(n=8),H2S-intoxicated model group(n=-40),and UTI treatment group(n=40).The H2 S-intoxicated model group and UTI treatment group were exposed to H2S (283.515 mg/m3)by inhalation for 1h,then UTI treatment group was intraperitoneally exposed to UTI at the dose of l05 U/kg for 2 h.H2S-intoxicated model group and UTI treatment group were sacrificed at 2,6,12.24 and 48 h after exposure,respectively.The levels of malondialdehyde(MDA),superoxidedismutase(SOD),catalase (CAT),glutathioneperoxidase(GSH-Px)and glutathione(GSH)in the rat lung tissues were measured.The expression levels of Nrf2 mRNA in the rat lung tissues were detected.Pathological changes of rat lung tissues were observed under a light microscope and the lung injury scores were evaluated.Results Compared with control group,the pulmonary SOD,CAT and GSH levels at 2,6 and 12 h after exposure and the pulmonary GSH-Px levels at 2,6,12 and 24 h after exposure in H2S-intoxicated model group significantly decreased(P＜0.05 or P＜0.01).The levels of pulmonary MDA at 2,6,12 and 24 h after exposure in H2S-intoxicated model group were significantly higher than those in normal control group(P＜0.01).As compared with H2S-intoxicated model group,the pulmonary GSH-Px activities at 6 and 12 h after exposure,the pulmonary CAT activities at 2,6 and 12 h after exposure,the pulmonary GSH levels at 2,6,12 and 24 h after exposure and the pulmonary SOD activities at 2,6,12,24 and 48 h after exposure in UTI treatment group significantly increased(P＜0.05 or P＜0.01),the pulmonary MDA levels at 2,6 and 12 h after exposure in UTI treatment group significantly decreased(P＜0.01).The expression levels of Nrf2 mRNA at 2,6,12,24 h after exposure in H2S-intoxicated model group were 0.314±0.011,0.269±0.010,0.246±0.011 and 0.221 ±0.018,respectively,which were significantly higher than those(0.149 ±0.012)in control group(P＜0.01).As compared with H2S-intoxicated model group,the expression levels(0.383±0.017,0.377±0.014,0.425±0.017,0.407±0.011 and 0.381±0.010)of Nrf2 mRNA at 2,6,12,24and 48 h after exposure in UTI treatment group significantly increased(P＜0.01).The lung injury at 24 h after exposure in H2S-intoxicated model group was higher than that in UTI treatment group.Histopathological examination showed that the scores of lung injury at 12,24 and 48 h after exposure in UTI treatment group was significantly lower than those in H2S-intoxicated model group(P＜0.01).Conclusion Oxidative stress and Nrf2 activation may be the important factors in rat lung injury induced by H2S-intoxicated,UTI may reduce the rat lung injury and protect the rat lung from damage induced by H2S by inhibiting ROS,improving he imbalance in redox and up-regulating Nrf2 mRNA expression.
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