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慢性阻塞性肺疾病患者HO-1基因启动子微卫星多态性与凋亡的关系研究

A study on the relationship between the microsatellite polymorphism in the heme oxygenase-1 gene promoter and cell apoptosis in the lung tissue from patients with COPD

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【作者】 马志明张珍祥韩泽民徐永建

【Author】 MA Zhi-Ming,ZHANG Zhen-Xiang,HAN Ze-Min,et al.Department of Respiratory Medicine,Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China

【机构】 华中科技大学同济医学院附属同济医院呼吸内科华中科技大学同济医学院附属同济医院呼吸内科 湖北武汉430030湖北武汉430030湖北武汉430030

【摘要】 目的探讨HO-1基因启动子微卫星多态性与COPD易感性的关系。方法利用PCR基因扩增,聚丙烯酰胺凝胶电泳及硝酸银染色及原位缺口末端DNA碎片标记技术分析50例COPD患者和30例未合并COPD组肺组织(对照组)HO-1基因启动子5’端(GT)n重复序列不同基因型与肺组织不同细胞凋亡的关系。结果(1)COPD组肺组织细胞凋亡指数显著高于对照组(包括吸烟的对照组和不吸烟的对照组,P<0.05,P<0.01)。吸烟的对照组肺组织细胞凋亡指数亦高于不吸烟的对照组(P<0.01)。(2)COPD组L型等位基因频率显著高于对照组(P<0.05)。(3)含有L型等位基因的基因型的样本其肺组织细胞凋亡指数显著高于不含L型等位基因的基因型的样本(均P<0.01)。结论(1)吸烟可能是引起细胞凋亡的重要因素。(2)HO-1基因启动子5’端大量(GT)n重复序列的个体可能抑制吸烟引起的氧化应激对HO-1基因的诱导性表达,使其肺组织凋亡细胞数目增加,导致肺组织破坏而与COPD的易感性相关。

【Abstract】 Objective To investigate the correlation between microsatellite polymorphism in the heme oxygenase-1(HO) gene promoter and susceptibility to the chronic obstructive pulmonary disease(COPD).Methods The relationship between the different genotypes of(GT) n repeats in the heme oxygenase-1 gene promoter and cell apoptosis in the lung tissue from 50 cases of patients with COPD and 30 cases with out COPD(control group) with the techniques of polymerase chain reaction(PCR),polyacrylamide gel electrophoresis,silver stain and in situ end label for the detection of DNA fragment of apoptosis cells.Results (1) The average apoptotic index in the lung tissues of COPD group was significantly higher than that of the control groups with and without smoking history(P<0.05,P<0.01,respectively).A statistical deference of average apoptotic indexes was observed between the control group with smoking history and without smoking history(P<0.01).(2) The frequency of class L alleles in COPD group was significantly higher than that of the control group(P<0.05).(3) The average apoptotic index of the lung tissue in the subjects with a class L allele was significantly higher compared with that of the subjects without a class L allele(P<0.01,respectively).Conclusions (1) Smoking may be play an important role in the cell apoptosis of the lung tissue.(2) The genotypes with ≥ 30 GT repeats in the HO-1 gene promoter may inhibit the expressive levels of HO-1 gene induced by oxidative stress caused by smoking,increase the apoptotic cells in lung tissue,and then result in destruction of lung tissue which may be related to the susceptibility to COPD.

【基金】 国家科技攻关计划项目〔2001BA703B03(B)〕;卫生部部属临床学科重点项目(学科代码3202060)资助
  • 【文献出处】 中国老年学杂志 ,Chinese Journal of Gerontology , 编辑部邮箱 ,2005年11期
  • 【分类号】R563.9
  • 【被引频次】6
  • 【下载频次】184
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