刁瑞英,宋良文,王少霞,尹纪业.Ⅳ型胶原、MMPs和TIMPs在放射性肺损伤重建中的作用[J].中华放射医学与防护杂志,2007,27(6):517-520
Ⅳ型胶原、MMPs和TIMPs在放射性肺损伤重建中的作用
Effect of collagen type Ⅳ,MMPs and TIMPs on remodeling of radiation pulmonary injury
投稿时间:2006-11-30  
DOI:
中文关键词:  肺损伤  重建  Ⅳ型胶原  MMP  TIMP
英文关键词:Pulmonary injury  Remodeling  Collagen type Ⅳ  MMPs  TIMPs
基金项目:国家自然科学基金资助项目(30570545)
作者单位E-mail
刁瑞英 100850 北京, 军事医学科学院放射与辐射医学研究所  
宋良文 100850 北京, 军事医学科学院放射与辐射医学研究所 Lsong1@yahoo.com 
王少霞 100850 北京, 军事医学科学院放射与辐射医学研究所  
尹纪业 100850 北京, 军事医学科学院放射与辐射医学研究所  
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中文摘要:
      目的 探讨Ⅳ型胶原、基质金属蛋白酶(MMPs)及其组织基质金属蛋白酶抑制剂(TIMPs)在放射性肺损伤早期重建中的作用。方法 用20 Gy 60Co γ 射线照射大鼠右胸部, 建立放射性肺损伤模型,1、2、4 周后分别取材;用实时荧光定量PCR和免疫组织化学方法,从基因表达和蛋白质合成水平结合图像分析对肺组织Ⅳ型胶原、MMP-2、MMP-9、TIMP-1和TIMP-2 mRNA进行定量分析。结果 实时定量PCR基因检测:Ⅳ型胶原表达于1周时升高,2周时下降;MMP-2在2周时达高峰,与Ⅳ型胶原成相反变化趋势;MMP-9呈明显的升高、下降、再升高趋势,与Ⅳ型胶原变化趋势相同;TIMP-1 表达较低,各时间点之间无明显差异;TIMP-2 呈现略升高、降低、升高趋势,与MMP-2表达相反。免疫组化-图像分析:肺组织Ⅳ型胶原含量于1周即明显增加,2周开始下降;MMP-2在2周时下降,随后升高,后期与Ⅳ型胶原呈相反趋势;MMP-9变化趋势同Ⅳ型胶原,但程度明显高于后者;TIMP-1于2周时轻度升高,与MMP-9趋势相反。结论 Ⅳ型胶原、MMP-2 和MMP-9及其组织抑制物参与放射性肺损伤早期的无效重建过程,MMP-2和MMP-9具有降解Ⅳ型胶原作用;Ⅳ型胶原降解障碍可能与肺纤维化启动有一定关系。
英文摘要:
      Objective To explore the effect of collagen type Ⅳ, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs(TIMPs) on early remodeling after radiation pulmonary injury.Methods Right lungs of rats were irradiated by 60Co γ-rays at a dose of 20 Gy to induce radiation pulmonary injury, and the lung specimens were taken at weeks 1, 2, 4 after irradiation. Quantitative analysis was performed on pulmonary collagen type Ⅳ, MMP-2, MMP-9, TIMP-2, TIMP-1 at the level of gene expression and protein synthesis using real-time PCR or immunohistochemistry.Results Gene detection using real-time PCR: gene expression of collagen type Ⅳ increased at week 1 and decreased at week 2 after irradiation; MMP-2 reached peak at week 2 in which an opposed alteration trend was displayed; MMP-9 appeared a significant trend of elevation, then decrease and elevation again which was similar to those of collagen type Ⅳ; expression of TIMP-1 was lower, and there was no marked difference among all time points; TIMP-2 displayed a trend of slight elevation, then decrease and elevation again, which was opposed to MMP-2. Immunohistochemistry-image analysis: Pulmonary collagen type Ⅳ obviously increased at week 1, and began to decrease at week 2; MMP-2 decreased at week 2 and then increased;an opposed alteration trend to that of collagen type Ⅳ was displayed; alteration trend of MMP-9 was similar to that of collagen type Ⅳ but the extent was higher; gene expression of TIMP-1 slightly increased at 2 week and an opposed trend to of MMP-9 was displayed.Conclusions Collagen type Ⅳ, MMP-2, MMP-9 and their tissue inhibitors were involved in ineffective remodeling in the early radiation pulmonary injury; MMP-2 and MMP-9 play an important role in degradation of collagen type Ⅳ; Disturbance of collagen type Ⅳ degradation might have relationship with the initiation of pulmonary fibrosis.
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