壹期煤工尘肺患者血清p53和Bcl-2水平及意义
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摘要
目的探讨壹期煤工尘肺(CWP)患者血清肿瘤蛋白53(p53)、B淋巴细胞瘤-2蛋白(Bcl-2)水平变化及意义。方法用酶联免疫法检测88例壹期CWP患者(CWP组)、53例井下健康煤矿工人(接尘组)及35例井上健康工人(非接尘组)血清p53和Bcl-2水平。结果与非接尘组和接尘组比较,CWP组p53和Bcl-2水平均升高,差异均有统计学意义(均P<0.01);接尘组Bcl-2水平高于非接尘组,差异有统计学意义(P<0.01),p53水平无明显变化(P>0.05);CWP患者中>30年接尘时间组Bcl-2水平高于<20年接尘时间组,差异有统计学意义(P<0.05)。CWP患者血清p53和Bcl-2水平呈轻度正相关(rs=0.263,P<0.05)。结论壹期CWP患者血清p53和Bcl-2水平升高与尘肺发生发展有关;Bcl-2水平改变可能与接尘时间有关。
[Objective]To explore the changes and significance of serum tumor protein 53(p53) and B-cell lymphoma-2(Bcl-2)in patients with stage Ⅰ coal workers' pneumoconiosis( CW P).[Methods] Serum levels of p53 and Bcl-2 were determined in 88 CWP patients( CWP group), 53 healthy undergr ound coal workers(dust-exposed group) 35 healthy ground workers(non-dust exposed group) by ELISA.[Results]Serum levels of p53 and Bcl-2 in CWP group were significantly higher than those in dustexposed group and non-dust-exposed group(all P<0.01). Bcl-2 level in dust-exposed group were significantly higher than that in non-dust-exposed(P<0.01), and the difference in p53 level was not statistically significant(P>0.05). In CWP group, Bcl-2 level in patients with dust-exposed durations more than 30 years was higher than that in those with dust-exposed durations less than 20 years(P<0.05). In CWP patients, there was a slight positive correlation between p53 level and Bcl-2 level(rs=0.263, P<0.05).[Conclusion]In stageⅠpatients, the serum levels of p53 and Bcl-2 are elevated and associated with the development of the CWP. The changes of the serum Bcl-2 level may be related to the dust-exposed durations.
[Objective]To explore the changes and significance of serum tumor protein 53(p53) and B-cell lymphoma-2(Bcl-2)in patients with stage Ⅰ coal workers' pneumoconiosis( CW P).[Methods] Serum levels of p53 and Bcl-2 were determined in 88 CWP patients( CWP group), 53 healthy undergr ound coal workers(dust-exposed group) 35 healthy ground workers(non-dust exposed group) by ELISA.[Results]Serum levels of p53 and Bcl-2 in CWP group were significantly higher than those in dustexposed group and non-dust-exposed group(all P<0.01). Bcl-2 level in dust-exposed group were significantly higher than that in non-dust-exposed(P<0.01), and the difference in p53 level was not statistically significant(P>0.05). In CWP group, Bcl-2 level in patients with dust-exposed durations more than 30 years was higher than that in those with dust-exposed durations less than 20 years(P<0.05). In CWP patients, there was a slight positive correlation between p53 level and Bcl-2 level(rs=0.263, P<0.05).[Conclusion]In stageⅠpatients, the serum levels of p53 and Bcl-2 are elevated and associated with the development of the CWP. The changes of the serum Bcl-2 level may be related to the dust-exposed durations.
引文
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[18]RICCI A,CHERUBINI E,SCOZZI D,et al.Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts[J].J Cell Physiol,2013,228(7):1516-1524.
[19]SANDERS YY,LIU H,ZHANG X Y,et al.Histone modifications in Senescence-Associated resistance to apoptosis by oxidative stress[J].Redox Biol,2013,1(1):8-16.
[20]PLATAKI M,KOUTSOPOULOS AV,DARIVIANAKI K,et al.Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis[J].Chest,2005,127(1):266-274.
[2]HUAUX F.New developments in the understanding of immunology in silicosis[J].Curr Opin Allergy Clin Immunol,2007,7(2):168-173.
[3]WANG LY,BOWMAN L,LU YJ,et al.Essential role of p53 in silicainduced apoptosis[J].Am J Physiol Lung Cell Mol Physiol,2005,288(3):L488-L496.
[4]SHETTY SK,TIWARI N,MARUDAMUTHU AS,et al.p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis[J].Am J Pathol,2017,187(5):1016-1034.
[5]SAFAEIAN L,ABED A,VASEGHI G.The role of Bcl-2 family proteins in pulmonary fibrosis[J/OL].Eur J Pharmacol,2014,741:281-289[2018-06-06].https://www.chinapubmed.net/25058906.DOI:10.1016/j.ejphar.2014.07.029.
[6]陈尚雅,崔冠群,贾强,等.染矽尘大鼠差异性表达基因生物信息学分析[J].中国职业医学,2017,44(2):181-187.
[7]孙晓芳,段斐,牛建昭,等.三七总皂苷对肺纤维化小鼠细胞凋亡及Bax/Bcl-2表达的影响[J].重庆医学,2013,42(10):1125-1127.
[8]陈国萍,李家宁,丛莹莹.N-乙酰半胱氨酸对肺纤维化大鼠Bcl-2/Bax的影响[J].现代医学,2012,40(4):383-390.
[9]中华人民共和国卫生部.尘肺病诊断标准:GBZ 70-2009[S].北京:中国标准出版社,2009.
[10]YOUNGERST,RINNJL.p53regulatesenhanceraccessibilityandactivity in response to DNA damage[J].Nucleic Acids Res,2017,45(17):9889-9900.
[11]AKRAM KM,LOMAS NJ,FORSYTH NR,et al.Alveolar epithelial cells in idiopathic pulmonary fibrosis display upregulation of TRAIL,Dr4 and Dr5 expression with simultaneous preferential over-expression of pro-apoptotic marker p53[J].Int J Clin Exp Pathol,2014,7(2):552-564.
[12]LIU H,FANG S,WANG W,et al.Macrophage-derived MCPIP1mediates silica-induced pulmonary fibrosis via autophagy[J].Part Fibre Toxicol,2016,13(1):55-71.
[13]WANG W,LIU H,DAI X,et al.p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis[J/OL].Sci Rep,2015,5:16900-16911[2018-06-06].https://www.chinapubmed.net/26576741.DOI:10.1038/srep16900.
[14]符跃强,卢仲毅,方芳,等.p53在氧化应激下肺泡Ⅱ型上皮细胞凋亡中的作用[J].第四军医大学学报,2009,30(24):2952-2955.
[15]GAHL RF,DWIVEDI P,TJANDRA N.Bcl-2 proteins bid and bax form a network to permeabilize the mitochondria at the onset of apoptosis[J].Cell Death Dis,2016,7(10):e2424-2434.
[16]BUDINGER GR,MUTLU GM,EISENBART J,et al.Proapoptotic bid is required for pulmonary fibrosis[J].Proc Natl Acad Sci USA,2006,103(12):4604-4609.
[17]陈伟,欧阳劭,唐双阳,等.肺纤维化鼠细胞凋亡及Fas/Bcl-2动态变化[J].中南医学科学杂志,2012,40(2):139-143.
[18]RICCI A,CHERUBINI E,SCOZZI D,et al.Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts[J].J Cell Physiol,2013,228(7):1516-1524.
[19]SANDERS YY,LIU H,ZHANG X Y,et al.Histone modifications in Senescence-Associated resistance to apoptosis by oxidative stress[J].Redox Biol,2013,1(1):8-16.
[20]PLATAKI M,KOUTSOPOULOS AV,DARIVIANAKI K,et al.Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis[J].Chest,2005,127(1):266-274.