PAI-1基因多态性对支气管哮喘气道重塑影响的研究  

Role of the 4G/5G polymorphism of the PAI-1 gene in airway remodeling

作　　者：张晓岩[1] 林江涛[1] 李香凝[1] 杨萌[1] 俞红霞[1] 李桂琴[1] 黄小杰[1] 王萍[1] 张岚[1] 周童亮[1] 舒峻[1] 

机构地区：[1]卫生部中日友好医院呼吸内科,北京100029

出　　处：《中华哮喘杂志（电子版）》2007年第2期69-74,共6页Chinese Journal of Asthma(Electronic Version)

摘　　要：目的探讨纤溶酶原激活物抑制剂-1(PAI-1)基因启动子-675 4G/5G多态性对支气管哮喘(简称哮喘)气道重塑的影响。方法将慢性持续期哮喘患者(330例)和健康人(20名)分列为哮喘组和对照组,提取所有受试者全血DNA,用等位基因特异性PCR(ASO)法测定PPAI-1启动子区域-675位点多态性,酶联免疫吸附试验(ELISA)法测定血浆PAI-1、血浆转化生长因子β_1(TGF-β_1)和基质金属蛋白酶9(MMP-9)水平,高分辨率CT(HRCT)观察所有受试者肺部影像学特征,运用PickerPQ6000分析软件测定气道壁厚度(T)、气道壁面积(WA),采用气道壁厚度/气道外径(T/D)和气道壁面积占气道总面积百分比(WA%)作为标化指标。结果 WA轻度哮喘组(13.27±4.06)mm^2和中重度哮喘组(13.86±4.88)mm^2与健康对照组(9.43±3.70)mm^2比较,有统计学差异(P均<0.05),但轻度哮喘组和中重度哮喘组差异无显著性(P=0.768)。WA%值轻度哮喘组(71.30±6.55)%和中重度哮喘组(72.03±8.34)%,与对照组(66.24±5.19)%比较显著增加(P均<0.05);轻度哮喘组与中重度哮喘组之间无统计学意义。T、T/D差异无显著性(P=0.857,P=0.967)。血浆TGF-β_1中重度哮喘组(69.86±11.71)pg/ml显著高于轻度哮喘组(59.40±11.35)pg/ml和对照组(59.29±13.53)pg/ml(P<0.05),但轻度哮喘组和对照组之间差异无显著性(P=0.981);血浆MMP-9水平对照组、轻度哮喘组、中重度哮喘组之间无统计学差异(F=0.388,P=0.68)。4G/4G、4G/5G和5G/5G基因型表达的TGF-β_1、T和WA%差异有统计学意义(P<0.05)。血浆PAI-1仅与血浆TGF-β_1存在相关关系(r=0.335,P<0.05),与T、T/D、WA和WA%无相关关系(P>0.05)。多元方差分析显示PAI-1基因多态性、血浆TGF-β_1、血浆PAI-1水平与PAI-14G/5G基因多态性的交互作用对气道重塑表型的影响有统计学意义(P=0.059,P=0.026,P=0.030)。结论哮喘患者存在气道壁增厚、气道壁面积增加等气道重塑表现。PAI-1启动子4G/5G多态性可能是哮喘气道重塑的独立Objective To explore the possible roles of-675 4G/5G PAI-1 polymorphism in asthmatic remodeling. Methods Genomic DNA was isolated from the peripheral blood of 30 chronic persistent asthmatics and 20 heahhy subjects. The PAl 1 4G/5G genotypes were determined by an allele-specific polymerase chain reaction. Everyone performed HRCT for the evaluation of the severity of asthma and airway remodeling. Quantitative assessment was used to analyze the thickness of airway wall （T,T/D） and airway wall area （WA,WA%）. Levels of PAI -1,TGF-β1, and MMP-9 in plasma were detected by ELISA. Results Comparison of Groupl （mild persistent asthma,） and Group 2 （moderate and severe persistent） asthma with 20 control subjects revealed significantly higher values of WA （13.27±4.06） mm^2 for Group 1,（13.86±4.88） mm^2 for Group 2 and （9.43±3.70） mm^2 for controls（P〈0.05） and WA~ （71.30±6.55）% ,（72.03±8.34）% and （66.24±5. 19）% （P〈 0.05） ,respectively. There was no significant difference between asthmatic subgroups. T and T/D of asthmatic patients were higher than control subjects, but had no statistically significa＇nt differences （ P 〉0. 05）. Compare with group 2 （69.86±11.71） pg/ml,plasma TGF -β1 levels in group1（59.40± 11.35） pg/ml and control subjects （59.29 ± 13.53） pg/ml decreased significantly （ P 〈5 0.05）. Although levels of plasma MMP 9 in asthmatics were higher than those in controls,the increase was not significant（ F =0. 388, P〉0.05）. Levels of TGF-β1 ,T and WA% for 4G/4G were significantly higher than for those of other genetypes （ F = 15. 575,11. 263,0. 037 ; P 〈0.05）. I.evels of TGF-β1 ,T and WA% for 4G/4G genotype were significantly higher than those of 4G/5G and 5G/5G genotype （ P〈 0.05）. Morning plasma PAI -1 concentration correlated significantly with TGF -β1 （ r =0. 335, P 〈0.05） ,but not with T,T/D,WA and WA%（ P 〉0.05）. Multivariate analysis of variance using T, T/D,WA,WA% as dependent variables and

关 键 词：纤溶酶原激活物抑制剂1 基因多态性 气道重塑 高分辨率CT 

分 类 号：R562.25[医药卫生—呼吸系统] R541.4[医药卫生—内科学]