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百草枯致小鼠肺间质纤维化过程中Smad3蛋白的表达 被引量:5

Expression of Smad3 protein during the pulmonary fibrosis induced by paraquat in mice
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摘要 目的使用免疫组织化学的方法观察百草枯(paraquat,PQ)致小鼠肺间质纤维化过程中Smad3蛋白的表达。方法 58只雄性C57BL/6J小鼠随机分组。实验组48只,通过腹腔注射10 mg/kg PQ建立小鼠肺间质纤维化模型,对照组10只,腹腔注射等量生理盐水。小鼠在实验组染毒后第2、5、7、14天和对照组第7天时分别被安乐死,留取肺组织标本。标本进一步进行HE染色和Smad3蛋白的免疫组化研究。结果光镜观察小鼠染毒后第2~5天肺组织出现水肿、出血、炎症细胞浸润等改变,第7天有少量胶原沉积及斑片状的纤维化表现,第14天表现更加明显。免疫组化观察染毒小鼠肺组织Smad3蛋白表达,第2~7天肺中巨噬细胞和部分II型肺泡上皮细胞的细胞核中见到阳性表达。Smad3阳性表达和巨噬细胞数量呈正相关。第14天,在成纤维细胞灶增生的成纤维细胞核中,也可见到Smad3弱阳性表达。结论在PQ致肺间质纤维化过程中,Smad3蛋白异常表达并对肺纤维化的发生发展具有重要的作用。 Objective The expression of Smad3 protein in the pulmonary fibrosis induced by paraquat (PQ) was detected by immunohistochemistry. Methods 57BL/6J male mice (n = 58)were divided randomly into the experimental group and control group. Pulmonary fibrosis was induced by intraperitonea] injection of PQ( 10 mg/kg) in the experimental group( n = 48) , while physiological saline was used in the control group( n = 10)by the same method. The mice were sacrificed ori days 2, 5, 7 and 14 in the experimental group and the control ones on day 7. The lungs were taken for histological examinatioon using HE staining and the expression of Smad3 protein was determined by immunohistochemistry. Resuits The histological changes including edema, hemorrhage and inflammatory cell infiltration were seen in the lung tissues of mice after PQ administration on days 2 and 5. There were slight collagen deposition and plaque-like fibrosis on day 7 and apparent fibrosis on day 14. The Smad3-positive signs appeared in the nucli of infiltrating macrophages and many type II alveolar epithelial cells on days 2, 5 and 7. The positive expression of Smad3 proteins was positively correlated with the amount of infiltrating macrophages. On day 14 the faint Smad3-positive expression was detected in the nuclei of fibroblasts in hyperplastic foci. Conclusions The expression of Smad3 protein is abnormal during pulmonary fibrosis induced by PQ and Smad3 plays an important role in the development of pulmonary fibrosis.
出处 《中国实验动物学报》 CAS CSCD 2012年第1期88-90,共3页 Acta Laboratorium Animalis Scientia Sinica
基金 辽宁省教育厅基金资助项目(2008785) 高等学校博士学科点专项科研基金课题(20092104110001)
关键词 百草枯 中毒 肺间质纤维化 SMAD3 免疫组化 小鼠 Paraquat Intoxication Pulmonary fibrosis Smad3 Immunohistochemistry mice
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参考文献12

  • 1Onyon LJ,Volans GN.The epidemiology and prevention of paraquat poisoning[J].Human Toxicol,1987,6(1):19-29.
  • 2Zhao Y,Geverd DA.Regulation of Smad3 expression in bleomycin-induced pulmonary fibrosis:a negative feedback loop of TGF-beta signaling[J].Biochem Biophys Res Commun 2002,294(2):319-23.
  • 3董雪松,刘盛业,刘伟,刘淑英,刘志.腹腔一次注射法构建百草枯致小鼠肺间质纤维化模型[J].中国实验动物学报,2011,19(4):351-353. 被引量:6
  • 4Ishida Y,Takayasu T,Kimura A,et al.Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice[J].Legal Med,2006,8(2):102-109.
  • 5Mainwaring G,Lim FL,Antrobus K,et al.Identification of early molecular pathways affected by paraquat in the rat lung[J].Toxicology,2006,225 (2-3):157-172.
  • 6Groneberg DA,Witt H,Adcock IM,et al.Smads as intracellular mediators of airway inflammation[J].Exp Lung Res,2004,30 (3):223-50.
  • 7Zhao J,Shi W,Wang YL,et al.Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice[J].Am J Physiol Lung Cell Mol Physiol,2002,282(3):L585-93.
  • 8Bonniaud P,Kolb M,Galt T,et al.Smad3 null mice develop airspace enlargement and are resistant to TGF-beta-mediated pulmonary fibrosis[J].J Immunol,2004,173 (3):2099-2108.
  • 9Roberts AB,Tian F,Byfield SD,et al. Smad3 is key to TGF-beta-mediated epithelialto-mesenchymal transition, fibrosis,tumor suppression and metastasis[J].Cytokine Growth Factor Rev,2006,17(1-2):19-27.
  • 10Uhal BD, Kim JK, Li X, et al. Angiotensin-TGF-beta 1 crosstalk in human idiopathic pulmonary fibrosis: autocrine mechanisms in myofibroblasts and macrophages[J].Curr Pharm Des,2007,13(12):1247-56.

二级参考文献19

  • 1佟飞,田英平,石汉文,姚冬奇,霍书花,苏建玲,扈琳,陈慧.急性百草枯中毒大鼠肺组织中基质金属蛋白酶及其组织抑制剂表达变化的研究[J].中国急救医学,2006,26(1):41-43. 被引量:52
  • 2佟飞,田英平,石汉文,崔炜,陈慧,高恒波,刘力斗,王霞.急性百草枯中毒大鼠肺组织核因子-κB及诱导型一氧化氮合酶表达变化的研究[J].中国急救医学,2006,26(7):520-522. 被引量:36
  • 3Lee EY, Hwang KY, Yang JO, et al. Paraquat intoxication in Korea [J]. Arch Environ Health, 2002 , 57 ( 2 ) :162 -166.
  • 4Bismuth C, Gamier R, Baud F J, et al. Paraquat poisoning. An overview of the current status [J]. Drug Saf, 1990, 5 (4) : 243 -51.
  • 5Suntres ZE. Role of antioxidants in paraquat toxicity [ J]. Toxicology, 2002, 180 (1) :65 -77.
  • 6Yeh ST, Guo HR, Su YS, et al. Protective effects of N-acetylcysteine treatment post-acute paraquat intoxication in rats and in human lung epithelial cells [ J ]. Toxicology, 2006, 223 (3) : 181 - 190.
  • 7Ishida Y,Takayasu T, Kimura A, et al. Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice[J]. LegalMed, 2006, 8(2) :102 -109.
  • 8Satomi Y, Sakaguchi K, Kasahara Y, et al. Novel and extensive aspects of paraquat-induced pulmonary fibrogenesis: comparative and time-course microarray analyses in fibrogenic and non-fibrogenic rats[J]. J Toxic Sci, 2007, 32(5) :529 -553.
  • 9Epperly MW,Guo H,Gretton JE,et al.Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis[J].Am J Respir Cell Mol Biol,2003,29:213
  • 10Kasai H,Allen JT,Mason RM,et al.TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT)[J].Respir Res,2005,6:56

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