Expressions of matrix metalloproteinase-16, autophagy-related gene 5 and autophagy-related gene 7 in children with bronchial asthma and their correlations with pulmonary function
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摘要:目的 探讨支气管哮喘患儿外周血单个核细胞中基质金属蛋白酶-16(MMP-16)、自噬相关基因5( ATG5 )、自噬相关基因7( ATG7 )表达水平与肺功能的相关性。方法 选取哮喘患儿80例作为观察组，健康体检儿童80例作为对照组。采集观察组和对照组患儿血样，检测第1秒用力呼气容积占预计值百分比(FEV1%)、用力肺活量(FVC)、最大呼气峰流速占预计值百分比(PEF%), 计算第1秒用力呼气容积占用力肺活量的比率(FEV1/FVC)。采用实时荧光定量聚合酶链反应(qRT-PCR)法检测外周血单个核细胞 MMP-16 mRNA、 ATG5 mRNA和 ATG7 mRNA水平; 采用Pearson法分析急性发作期哮喘患儿 MMP-16 mRNA、 ATG5 mRNA、 ATG7 mRNA与肺功能指标的相关性。结果 MMP-16 mRNA、 ATG5 mRNA、 ATG7 mRNA水平在对照组患儿和观察组临床缓解期患儿及急性发作期患儿中呈依次显著升高趋势(P<0.05); FEV1%、FEV1/FVC和PEF%在对照组患儿和观察组临床缓解期患儿及急性发作期患儿中呈依次显著降低趋势(P<0.05)。急性发作期哮喘患儿外周血单个核细胞 MMP-16 mRNA与 ATG5 mRNA、 MMP-16 mRNA与 ATG7 mRNA、 ATG5 mRNA与 ATG7 mRNA均呈显著正相关(r=0.536、0.542、0.534, P<0.05), 且 MMP-16 mRNA、 ATG5 mRNA、 ATG7 mRNA均与FEV1%、FEV1/FVC、PEF%呈显著负相关(P<0.05)。与轻度组比较，中重度组外周血单个核细胞 MMP-16 mRNA、 ATG5 mRNA、 ATG7 mRNA水平较高, FEV1%、FEV1/FVC、PEF%较低，差异有统计学意义(P<0.05)。结论 哮喘患儿外周血单个核细胞 MMP-16 mRNA、 ATG5 mRNA、 ATG7 mRNA水平较高，且均与肺功能有密切联系。Abstract:Objective To investigate the correlations of expression levels of matrix metalloproteinase-16 (MMP-16), autophagy-related gene 5 ( ATG5 ) and autophagy-related gene 7( ATG7 ) in peripheral blood mononuclear cells with pulmonary function in children with bronchial asthma.Methods Eighty children with asthma were selected as observation group, and eighty healthy children were selected as control group. Blood samples were collected from the observation group and control group, the forced expiratory volume in the first second as a percentage of the predicted value (FEV1%), forced vital capacity (FVC) and maximum peak expiratory flow as a percentage of the predicted value (PEF%) were detected, and ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) was calculated. Real-time fluorescent quantitative PCR (qRT-PCR) method was used to detect the levels of MMP-16 mRNA, ATG5 mRNA and ATG7 mRNA in peripheral blood mononuclear cells; Pearson method was used to analyze the correlations of MMP-16 mRNA, ATG5 mRNA and ATG7 mRNA with pulmonary function indexes in children with acute asthma.Results The levels of MMP-16 mRNA, ATG5 mRNA and ATG7 mRNA were significantly and successively increased in the control group and the children with clinical remission and acute attack in the observation group (P<0.05); FEV1%, FEV1/FVC and PEF% were significantly and successively reduced in the control group and the children with clinical remission and acute attack in the observation group (P<0.05). There were significant positive correlations between MMP-16 mRNA and ATG5 mRNA, MMP-16 mRNA and ATG7 mRNA, and ATG5 mRNA and ATG7 mRNA in peripheral blood mononuclear cells of children with acute asthma (r=0.536, 0.542, 0.534, P<0.05), and MMP-16 mRNA, ATG5 mRNA, ATG7 mRNA were negatively correlated with FEV1%, FEV1/FVC and PEF% (P<0.05). Compared with the mild group, the levels of MMP-16 mRNA, ATG5 mRNA and ATG7 mRNA in peripheral blood mononuclear cells of the moderate to severe group were significantly higher, while the FEV1%, FEV1/FVC and PEF% were significantly lower (P<0.05).Conclusion The levels of MMP-16 mRNA, ATG5 mRNA and ATG7 mRNA in peripheral blood mononuclear cells of children with asthma are higher, and these indexes are closely related to pulmonary function.
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图 1 急性发作期哮喘患儿外周血单个核细胞MMP-16 mRNA、ATG5 mRNA、ATG7 mRNA的相关性
A: MMP-16 mRNA与ATG5 mRNA的相关性; B: MMP-16 mRNA与ATG7 mRNA的相关性; C: ATG5 mRNA与ATG7 mRNA的相关性。
表 1 qRT-PCR引物序列
基因 上游引物5′-3′ 下游引物5′-3′ MMP-16 GTACGATACTCACAGCTGTAG CTCTAGCGTAGGTATGACTCG ATG5 CATATCAGAGTGCTAGATGCG GATCAATACATGCAGTCCTGG ATG7 CGTTGCAGCATGGACCATGG CTCTAGCGCTACGTAGTGCGTA GAPDH CGGGTCAGACCACTGCGAT CGGACCCATGACTGGTACCAG 
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表 2 观察组与对照组外周血单个核细胞MMP-16 mRNA、ATG5 mRNA和ATG7 mRNA水平比较(x±s)
组别 分期 MMP-16 mRNA ATG5 mRNA ATG7 mRNA 对照组(n=80) - 1.01±0.21 0.99±0.20 1.02±0.22 观察组(n=80) 临床缓解期 1.52±0.23* 1.73±0.28* 1.66±0.30* 急性发作期 2.73±0.34*# 3.02±0.38*# 2.64±0.32*# MMP-16: 基质金属蛋白酶-16; ATG5: 自噬相关基因5; ATG7: 自噬相关基因7。
与对照组比较, * P<0.05; 与临床缓解期比较, #P<0.05。
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表 3 观察组与对照组肺功能指标比较(x±s)
% 组别 分期 FEV1% FEV1/FVC PEF% 对照组(n=80) - 92.98±6.42 93.42±6.84 89.42±3.67 观察组(n=80) 临床缓解期 86.15±4.78* 85.42±5.71* 76.38±5.15* 急性发作期 65.24±4.71*# 73.05±6.38*# 58.66±6.13*# FEV1%: 第1秒用力呼气容积占预计值百分比; FEV1/FVC: 第1秒用力呼气容积占用力肺活量的比率;
PEF%: 最大呼气峰流速占预计值百分比。与对照组比较, * P<0.05; 与临床缓解期比较, #P<0.05。
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表 4 急性发作期哮喘患儿外周血单个核细胞MMP-16 mRNA、ATG5 mRNA、ATG7 mRNA与肺功能指标的相关性
指标 MMP-16 mRNA ATG5 mRNA ATG7 mRNA r P r P r P FEV1% -0.512 0.006 -0.524 0.004 -0.509 0.009 FEV1/FVC -0.496 0.008 -0.507 0.005 -0.517 0.006 PEF% -0.514 0.007 -0.513 0.002 -0.497 0.010 MMP-16 : 基质金属蛋白酶-16; ATG5: 自噬相关基因5; ATG7: 自噬相关基因7; FEV1%: 第1秒用力呼气容积占预计值百分比; FEV1/FVC: 第1秒用力呼气容积占用力肺活量的比率; PEF%: 最大呼气峰流速占预计值百分比。
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表 5 轻度组与中重度组外周血单个核细胞MMP-16 mRNA、ATG5 mRNA、ATG7 mRNA及肺功能指标比较(x±s)
组别 n MMP-16 mRNA ATG5 mRNA ATG7 mRNA FEV1%/% FEV1/FVC/% PEF%/% 轻度组 46 2.38±0.31 2.62±0.37 2.10±0.30 72.31±4.67 78.42±6.15 64.14±4.32 中重度组 34 3.20±0.34* 3.56±0.42* 3.37±0.35* 55.67±3.62* 65.78±5.20* 51.25±4.09* MMP-16 : 基质金属蛋白酶-16; ATG5: 自噬相关基因5; ATG7: 自噬相关基因7; FEV1%: 第1秒用力呼气容积占预计值百分比; FEV1/FVC: 第1秒用力呼气容积占用力肺活量的比率; PEF%: 最大呼气峰流速占预计值百分比。与轻度组比较, * P<0.05。
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