中华劳动卫生职业病杂志
中華勞動衛生職業病雜誌
중화노동위생직업병잡지
CHINESE JOURNAL OF INDUSTRIAL HYGIENE AND OCCUPATIONAL DISEASES
2013年
3期
178-183
,共6页
李冬%徐丽艳%常子娟%赵光举%南超%卢中秋
李鼕%徐麗豔%常子娟%趙光舉%南超%盧中鞦
리동%서려염%상자연%조광거%남초%로중추
百草枯%沙利度胺%急性肺损伤%NF-κB%肿瘤坏死因子%白细胞介素类
百草枯%沙利度胺%急性肺損傷%NF-κB%腫瘤壞死因子%白細胞介素類
백초고%사리도알%급성폐손상%NF-κB%종류배사인자%백세포개소류
Paraquat%Thalidomide%Acute lung injury%NF-κB%Tumor necrosisfactor%Interleukins
目的 探讨沙利度胺对百草枯诱导的小鼠急性肺损伤的干预作用及机制.方法 将雄性ICR小鼠随机分阴性对照组(30只)、沙利度胺药物对照组(30只)、百草枯中毒组(30只)和50、100、150 mg/kg剂量的沙利度胺干预组(各30只),阴性对照组:腹腔注射与染毒剂量相同体积的生理盐水；沙利度胺对照组:腹腔注射沙利度胺150 mg/kg；百草枯中毒组:腹腔注射百草枯溶液稀释液(22 mg/kg);沙利度胺干预组:腹腔注射等剂量百草枯溶液(22 mg/kg)染毒1h后,再分别注射50、100、150 mg/kg的沙利度胺.分别于不同处理1、3、7d后麻醉活杀小鼠,取肺组织.双抗夹心酶联免疫吸附法(ELISA)测定小鼠肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6等炎症因子水平；反转录聚合酶链式反应(PCR)测定NF-κB mRNA的表达；蛋白免疫印迹法(Western-blot)检测胞核内NF-κB P65的蛋白含量.光学显微镜下观察各实验组肺组织病理的表现；比较肺湿干重比.结果 与阴性对照组较,百草枯中毒组肺组织TNF-α、IL-1β、IL-6水平和NFκ-B mRNA、核内NF-κB蛋白量明显升高,肺湿干比也明显升高,差异均有统计学意义(P＜0.05).与百草枯中毒组比较,沙利度胺干预组肺组织TNF-α、IL-1β、IL-6水平和NF-κB mRNA、核内NF-κB蛋白量明显降低,肺湿干比明显降低,差异均有统计学意义(P＜0.05).150 mg/kg组沙利度胺干预组肺组织TNF-α、IL-1β、IL-6水平和NF-κB mRNA、核内NF-κB蛋白量降低最明显.病理学观察可见,百草枯中毒组在染毒后3d肺组织损害明显,沙利度胺干预组肺损害较百草枯中毒组有所减轻.结论 沙利度胺能减轻百草枯诱导的急性肺损伤和肺水肿,抑制NF-κB的激活及表达,下调TNF-α、IL-1β、IL-6等炎症因子水平可能是其作用机制之一.
目的 探討沙利度胺對百草枯誘導的小鼠急性肺損傷的榦預作用及機製.方法 將雄性ICR小鼠隨機分陰性對照組(30隻)、沙利度胺藥物對照組(30隻)、百草枯中毒組(30隻)和50、100、150 mg/kg劑量的沙利度胺榦預組(各30隻),陰性對照組:腹腔註射與染毒劑量相同體積的生理鹽水；沙利度胺對照組:腹腔註射沙利度胺150 mg/kg；百草枯中毒組:腹腔註射百草枯溶液稀釋液(22 mg/kg);沙利度胺榦預組:腹腔註射等劑量百草枯溶液(22 mg/kg)染毒1h後,再分彆註射50、100、150 mg/kg的沙利度胺.分彆于不同處理1、3、7d後痳醉活殺小鼠,取肺組織.雙抗夾心酶聯免疫吸附法(ELISA)測定小鼠肺組織腫瘤壞死因子-α(TNF-α)、白細胞介素(IL)-1β、IL-6等炎癥因子水平；反轉錄聚閤酶鏈式反應(PCR)測定NF-κB mRNA的錶達；蛋白免疫印跡法(Western-blot)檢測胞覈內NF-κB P65的蛋白含量.光學顯微鏡下觀察各實驗組肺組織病理的錶現；比較肺濕榦重比.結果 與陰性對照組較,百草枯中毒組肺組織TNF-α、IL-1β、IL-6水平和NFκ-B mRNA、覈內NF-κB蛋白量明顯升高,肺濕榦比也明顯升高,差異均有統計學意義(P＜0.05).與百草枯中毒組比較,沙利度胺榦預組肺組織TNF-α、IL-1β、IL-6水平和NF-κB mRNA、覈內NF-κB蛋白量明顯降低,肺濕榦比明顯降低,差異均有統計學意義(P＜0.05).150 mg/kg組沙利度胺榦預組肺組織TNF-α、IL-1β、IL-6水平和NF-κB mRNA、覈內NF-κB蛋白量降低最明顯.病理學觀察可見,百草枯中毒組在染毒後3d肺組織損害明顯,沙利度胺榦預組肺損害較百草枯中毒組有所減輕.結論 沙利度胺能減輕百草枯誘導的急性肺損傷和肺水腫,抑製NF-κB的激活及錶達,下調TNF-α、IL-1β、IL-6等炎癥因子水平可能是其作用機製之一.
목적 탐토사리도알대백초고유도적소서급성폐손상적간예작용급궤제.방법 장웅성ICR소서수궤분음성대조조(30지)、사리도알약물대조조(30지)、백초고중독조(30지)화50、100、150 mg/kg제량적사리도알간예조(각30지),음성대조조:복강주사여염독제량상동체적적생리염수；사리도알대조조:복강주사사리도알150 mg/kg；백초고중독조:복강주사백초고용액희석액(22 mg/kg);사리도알간예조:복강주사등제량백초고용액(22 mg/kg)염독1h후,재분별주사50、100、150 mg/kg적사리도알.분별우불동처리1、3、7d후마취활살소서,취폐조직.쌍항협심매련면역흡부법(ELISA)측정소서폐조직종류배사인자-α(TNF-α)、백세포개소(IL)-1β、IL-6등염증인자수평；반전록취합매련식반응(PCR)측정NF-κB mRNA적표체；단백면역인적법(Western-blot)검측포핵내NF-κB P65적단백함량.광학현미경하관찰각실험조폐조직병리적표현；비교폐습간중비.결과 여음성대조조교,백초고중독조폐조직TNF-α、IL-1β、IL-6수평화NFκ-B mRNA、핵내NF-κB단백량명현승고,폐습간비야명현승고,차이균유통계학의의(P＜0.05).여백초고중독조비교,사리도알간예조폐조직TNF-α、IL-1β、IL-6수평화NF-κB mRNA、핵내NF-κB단백량명현강저,폐습간비명현강저,차이균유통계학의의(P＜0.05).150 mg/kg조사리도알간예조폐조직TNF-α、IL-1β、IL-6수평화NF-κB mRNA、핵내NF-κB단백량강저최명현.병이학관찰가견,백초고중독조재염독후3d폐조직손해명현,사리도알간예조폐손해교백초고중독조유소감경.결론 사리도알능감경백초고유도적급성폐손상화폐수종,억제NF-κB적격활급표체,하조TNF-α、IL-1β、IL-6등염증인자수평가능시기작용궤제지일.
Objective To investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism.Methods Male ICR mice were randomly allocated to negative control group (n=30),thalidomide control group (n=30),paraquat poisoning group (n=30),50 mg/kg thalidomide treatment group (n=30),100 mg/kg thalidomide treatment group (n=30),and 150 mg/kg thalidomide treatment group (n=30).The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50,100,or 150 mg/kg) 1 h later.All mice were anesthetized and sacrificed at 1,3,or 7 d after paraquat poisoning,and their lung tissue was collected.The levels of tumor necrosis factor (TNF)-α,interleukin (IL)-1β,and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-κB p65 was measured by Western blot.The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated.Results Compared with the negative control group,the paraquat poisoning group had significantly increased levels of TNF-α,IL-1β,IL-6,NF-κB mRNA,and nuclear NF-κB p65and wet/dry ratio of the lung (P＜0.05).Compared with the paraquat poisoning group,the thalidomide treatment groups had significantly decreased levels of TNF-α,IL-1β,IL-6,NF-κB mRNA,and nuclear NF-κB p65 and =wet/dry ratios of the lung (P＜0.05),and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α,IL-1β,IL-6,NF-κB mRNA,and nuclear NF-κB p65.The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning,and the lung tissue damage was lessened in the thalidomide treatment groups.Conclusion Thalidomide can reduce paraquat-induced acute lung injury and lung edema.The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-et,IL-1 β,and IL-6.
