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中华实验和临床感染病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (01) : 46 -52. doi: 10.3877/cma.j.issn.1674-1358.2021.01.008

所属专题： 文献；

论著

手足口病患儿线粒体抗病毒蛋白和线粒体融合蛋白1表达及其临床意义
王沐淇1, 李亚萍1,†(), 冯丹丹1, 邓慧玲2, 张玉凤2, 王文俊1, 贾晓黎1, 党双锁1   
  1. 1. 710004　西安市，西安交通大学第二附属医院感染科
    2. 710003　西安市，西安市儿童医院感染科
  • 收稿日期:2020-06-08 出版日期:2021-02-15
  • 通信作者: 李亚萍
  • 基金资助:
    国家自然科学基金青年项目(No. 81701632); 陕西省科技项目(No. S2019-JC-QN-0055)

Expression and clinical significance of mitochondria antiviral signaling protein and mitochondria fusion protein of children with hand, foot and mouth disease

Muqi Wang1, Yaping Li1,†(), Dandan Feng1, Huiling Deng2, Yufeng Zhang2, Wenjun Wang1, Xiaoli Jia1, Shuangsuo Dang1   

  1. 1. Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
    2. Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an 710003, China
  • Received:2020-06-08 Published:2021-02-15
  • Corresponding author: Yaping Li
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引用本文：

王沐淇, 李亚萍, 冯丹丹, 邓慧玲, 张玉凤, 王文俊, 贾晓黎, 党双锁. 手足口病患儿线粒体抗病毒蛋白和线粒体融合蛋白1表达及其临床意义[J]. 中华实验和临床感染病杂志(电子版), 2021, 15(01): 46-52.

Muqi Wang, Yaping Li, Dandan Feng, Huiling Deng, Yufeng Zhang, Wenjun Wang, Xiaoli Jia, Shuangsuo Dang. Expression and clinical significance of mitochondria antiviral signaling protein and mitochondria fusion protein of children with hand, foot and mouth disease[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2021, 15(01): 46-52.

目的

检测线粒体抗病毒蛋白（MAVS）和线粒体融合蛋白1（MFN1）在手足口病（HFMD）患儿的表达水平，探索其在HFMD中的临床意义。

方法

选择2017年5月至2019年5月于西安交通大学第二附属医院感染科和西安市儿童医院就诊的82例HFMD患儿作为研究对象，将其按照病情严重程度和感染病原体不同分为EV71重症（18例）、EV71轻症（22例）、CA16重症（16例）和CA16轻症（26例），并以同期同年龄段体检儿童42例作为对照组。抽取手足口病患儿和对照组儿童外周血，检测并比较各组单个核细胞中MAVS和MFN1的mRNA相对表达量，采用单因素方差分析、两独立样本t检验分析各组研究对象MAVS和MFN1表达差异，以Spearman相关性分析MAVS和MFN1表达量与患者临床特征的相关性。

结果

MAVS在EV71型HFMD和CA16型HFMD患儿中相对表达量分别为（8.42 ± 2.27）%和（7.40 ± 2.34）%，均低于对照组MAVS相对表达量[（11.78 ± 3.42）%]，差异均有统计学意义（t = 3.450、P = 0.002，t = 4.512、P < 0.001）。但MAVS在EV71型HFMD组[重症vs.轻症：（8.07 ± 2.26）% vs. （8.71 ± 2.35）%，t = 0.611、P = 0.549）和CA16型HFMD组[重症vs.轻症：（7.58 ± 2.52）% vs. （7.29 ± 2.32）%，t = 0.270、P = 0.790]重症与轻症患儿中表达水平差异无统计学意义。MFN1在EV71型HFMD和CA16型HFMD患儿中相对表达量分别为（2.87 ± 1.20）%和（2.56 ± 1.22）%，均低于对照组儿童表达水平[（4.38 ± 1.28）%]，差异有统计学意义（t = 3.510、P < 0.001，t = 4.232、P < 0.001）。MFN1相对表达量在EV71型HFMD重症和轻症患儿中差异无统计学意义[重症vs.轻症：（2.44 ± 1.20）% vs. （3.22 ± 1.14）%，t = 1.492、P = 0.153]；但CA16型HFMD患儿MFN1相对表达量在重症和轻症病例组中差异有统计学意义[（3.23 ± 1.37）% vs. （2.15 ± 0.95）%，t = 2.150、P = 0.045]。MAVS相对表达水平与患儿年龄相关（r = 0.339、P = 0.030）；MFN1相对表达水平与患儿血糖水平（r = 0.442、P = 0.004）相关。

结论

MAVS和MFN1在手足口病患者中表达水平降低，MFN1高表达可能与CA16所致手足口病重症化有关。

关键词: 手足口病, 线粒体抗病毒蛋白, 线粒体融合蛋白, 先天免疫
Objective

To detect the expression levels of mitochondrial antiviral signaling protein (MAVS) and mitochondrial fusion protein 1 (MFN1) in children with hand, foot and mouth disease (HFMD), and to explore the clinical significances of HFMD.

Methods

Total of 82 children with HFMD were selected, including 18 cases with severe enterovirus 71 (EV71)-HFMD, 22 cases with mild EV71-HFMD, 16 cases with severe Coxsackievirus A16 (CA16)-HFMD and 26 cases with mild CA16-HFMD, while 42 healthy children of the same age range were selected as controls. Peripheral blood of these groups of children were obtained to detect and compare the mRNA expression levels of MAVS and MFN1 in mononuclear cells. MAVS and MFN1 expressions among different groups were analyzed by univariate variance analysis and t-test and the correlation between mRNA expression of the two indexes and clinical characteristics were analyzed by Spearman correlation analysis.

Results

The relative expression levels of MAVS of cases with EV71-HFMD and CA16-HFMD were [(8.42 ± 2.27)%] and [(7.40 ± 2.34)%], respectively, which were significantly lower than that of control group [(11.78 ± 3.42)], with significant differences (t = 3.450, P = 0.0016; t = 4.512, P < 0.001). However, there was no significant difference of MAVS expression levels of cases with severe HFMD and mild HFMD, either of cases with CA16 HFMD [severe vs. mild: (7.58 ± 2.52)% vs. (7.29 ± 2.32)%; t = 0.270, P = 0.790] or cases with EV71 HFMD [severe vs. mild: (8.07 ± 2.26)% vs. (8.71 ± 2.35)%; t = 0.611, P = 0.549]. The relative expression of MFN1 of cases with EV71-HFMD [(2.87 ± 1.20)%] and CA16-HFMD [(2.56 ± 1.22)%] were significantly lower than that of control group [(4.38 ± 1.28)%], with significant differences (t = 3.510, P < 0.001; t = 4.232, P < 0.001). The relative expression levels of MFN1 between cases with severe and mild EV71-HFMD were (2.44 ± 1.20)% and (3.22 ± 1.14)%, with significant difference (t = 1.492, P = 0.153). However, the relative expression of MFN1 in CA16-HFMD showed statistically significant difference between cases in severe group and mild group [(3.23 ± 1.37)% vs. (2.15 ± 0.95)%], with significant difference (t = 2.150, P = 0.045). MAVS relative expression level was correlated with age (r = 0.339, P = 0.030); MFN1 relative expression level was correlated with blood glucose level (r = 0.442, P = 0.004).

Conclusions

The expression levels of MAVS and MFN1 decreased in HFMD patients, and the high expression of MFN1 may be related to the severity of CA16-HFMD.

Key words: Hand, foot and mouth disease, Mitochondria antiviral signaling protein, Mitochondria fusion protein 1, Innate immunity
表1 MAVS和MFN1在各组研究对象的表达（±s，%）
组别 例数 MAVS MFN1
正常组 42 11.78 ± 3.42 4.38 ± 1.28
EV71感染组 40 8.42 ± 2.27 2.87 ± 1.20
  轻症 22 8.71 ± 2.35 3.22 ± 1.14
  重症 18 8.07 ± 2.26 2.44 ± 1.20
  t值   0.611 1.492
  P值   0.549 0.153
CA16感染组 42 7.40 ± 2.34 2.56 ± 1.22
  轻症 26 7.29 ± 2.32 2.15 ± 0.95
  重症 16 7.58 ± 2.52 3.23 ± 1.37
  t值   0.270 2.150
  P值   0.790 0.045
F值   12.166 9.925
P值   < 0.001 < 0.001
t正常组vs. EV71感染组   3.450 3.510
P正常组vs. CA16感染组   0.002 0.001
t正常组vs. CA16感染组   4.512 4.232
P正常组vs. CA16感染组   < 0.001 < 0.001
t EV71感染组vs. CA16感染组   1.421 0.813
PEV71感染组vs. CA16感染组   0.163 0.421
表2 不同临床特征HFMD患儿MAVS和MFN1的表达
临床特征 例数/数值 MAVS相对表达量（%） MFN1相对表达量（%）
性别      
  男 48 8.22 ± 1.95 2.76 ± 1.21
  女 34 7.44 ± 2.78 2.64 ± 1.24
t值   1.065 0.302
P值   0.294 0.765
年龄      
  ≤ 3岁 54 7.32 ± 2.14 2.46 ± 0.99
  > 3岁 28 9.01 ± 2.36 3.21 ± 1.46
t值   -2.327 -1.733
P值   0.025 0.099
出生体重      
  ≤ 2 500 g 6 7.04 ± 1.84 1.63 ± 0.65
  > 2 500 g 76 7.96 ± 2.38 2.80 ± 1.20
t值   -0.656 -1.652
P值   0.516 0.107
EV71      
  阴性 42 7.40 ± 2.34 2.56 ± 1.22
  阳性 40 8.42 ± 2.27 2.87 ± 1.20
t值   -1.421 -0.813
P值   0.163 0.421
呕吐      
  否 64 7.79 ± 2.12 2.72 ± 1.20
  是 18 8.29 ± 3.10 2.68 ± 1.31
t值   -0.573 0.099
P值   0.57 0.921
发热      
  否 4 5.82 ± 0.06 2.69 ± 0.82
  是 78 8.00 ± 2.34 2.71 ± 1.23
t值   -1.304 -0.031
P值   0.2 0.976
热程      
  ≤ 3 d 34 7.46 ± 1.86 2.37 ± 1.35
  > 3 d 48 8.21 ± 2.61 2.95 ± 1.05
t值   -1.017 -1.539
P值   0.316 0.132
体温（℃）      
  ≤ 38 4 5.82 ± 0.06 2.69 ± 0.82
  38～39 24 8.89 ± 2.40 2.65 ± 1.38
  > 39 54 7.61 ± 2.25 2.74 ± 1.18
F值   2.198 0.024
P值   0.125 0.976
易惊      
  否 44 8.34 ± 2.26 2.72 ± 1.11
  是 38 7.38 ± 2.38 2.70 ± 1.34
t值   1.322 0.048
P值   0.194 0.962
嗜睡      
  否 62 7.98 ± 2.44 2.83 ± 1.23
  是 20 7.30 ± 1.31 1.88 ± 0.55
t值   0.609 1.681
P值   0.546 0.101
惊厥      
  否 62 8.03 ± 2.59 2.68 ± 1.32
  是 20 7.47 ± 1.29 2.81 ± 0.79
t值   0.659 -0.302
P值   0.514 0.764
白细胞      
  ≤ 15 × 109/ml 70 7.91 ± 2.49 2.74 ± 1.12
  > 15 × 109/ml 12 7.83 ± 1.18 2.58 ± 1.74
t值   0.073 0.289
P值   0.942 0.774
中性粒细胞百分比
  ≤ 49.65% 41 7.98 ± 2.55 2.74 ± 1.11
  > 49.65% 41 7.81 ± 2.15 2.68 ± 1.33
t值 0.241 0.171
P值 0.811 0.865
淋巴细胞百分比
  ≤ 54.3% 41 7.58 ± 2.28 2.72 ± 1.22
  > 54.3% 41 8.20 ± 2.40 2.71 ± 1.23
t值   -0.846 0.035
P值   0.403 0.972
中性粒细胞/淋巴细胞
  ≤ 1.021 41 8.10 ± 2.69 2.83 ± 1.21
  > 1.021 41 7.68 ± 1.94 2.59 ± 1.22
t值   0.571 0.643
P值   0.572 0.524
血糖
  ≤ 6.60 mmol/L 46 7.65 ± 2.14 2.34 ± 0.95
  > 6.60 mmol/L 36 8.25 ± 2.61 3.24 ± 1.36
t值   -0.816 -2.351
P值   0.420 0.026
图1 MAVS和MFN1表达水平的相关性
图2 MFN1表达水平和血糖水平的相关性
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