血清过氧化物酶体增殖物激活受体和基质金属蛋白酶9水平与支原体肺炎患儿肠道菌群的相关性及其诊断价值

doi:10.19871/j.cnki.xfcrbzz.2023.04.005

摘要/Abstract

摘要： 目的探讨过氧化物酶体增殖物激活受体（PPARγ）和基质金属蛋白酶9（MMP-9）水平与支原体肺炎（MPP）患儿肠道菌群的相关性及其诊断价值,为MMP的诊疗提供新的方向。方法选取2021年1月至2023年1月在河间市人民医院儿科入院治疗的100例MPP患儿为研究对象,根据病程分为急性期组（48例）和恢复期组（52例）,并取同期于河间市人民医进行常规体检的健康儿童50例作为对照组,比较三组肠道菌群（大肠埃希菌、双歧杆菌、拟杆菌、肠球菌、乳酸杆菌）数量和血清PPARγ、MMP-9水平。Pearson相关性分析大肠埃希菌、双歧杆菌、拟杆菌、肠球菌、乳酸杆菌与血清PPARγ、MMP-9水平的相关性。Logistic回归分析急性期和恢复期MPP的影响因素;采用ROC曲线分析血清PPARγ、MMP-9及乳酸杆菌水平对急性期MPP的诊断价值。结果急性期组与恢复期组大肠埃希菌、肠球菌数量,以及血清MMP-9水平高于对照组,且急性期组高于恢复期组（P<0.05）;急性期组与恢复期组双歧杆菌、拟杆菌、乳酸杆菌数量,以及血清PPARγ水平低于对照组,且急性期组低于恢复期组（P<0.05）。Pearson相关性分析显示,大肠埃希菌、肠球菌数量与血清PPARγ水平呈负相关性（P<0.05）,双歧杆菌、拟杆菌、乳酸杆菌数量与血清PPARγ水平呈正相关性（P<0.05）;大肠埃希菌、肠球菌数量与血清MMP-9水平呈正相关性（P<0.05）,双歧杆菌、拟杆菌、乳酸杆菌数量与血清MMP-9水平呈负相关性（P<0.05）。Logistic回归分析显示,PPARγ是急性期、恢复期MPP发生的保护因素（P<0.05）,MMP-9是急性期、恢复期MPP发生的危险因素（P<0.05）,乳酸杆菌是急性期MPP发生的保护因素（P<0.05）。血清PPARγ、MMP-9、乳酸杆菌以及两者联合诊断急性期MPP的AUC分别为0.797、0.761、0.839、0.905,联合诊断的敏感度为93.24%,特异度为76.34%,三者联合优于血清PPARγ、MMP-9、乳酸杆菌各自单独诊断（Z三者联合-PPARγ=2.604,P<0.001;Z三者联合-MMP-9=3.310,P=0.007;Z三者联合-乳酸杆菌=2.810,P=0.008）。结论 MPP患儿血清PPARγ水平随着大肠埃希菌、肠球菌数量减少及双歧杆菌、拟杆菌、乳酸杆菌数量增加而升高,血清MMP-9水平随着大肠埃希菌、肠球菌数量增加及双歧杆菌、拟杆菌、乳酸杆菌数量减少而升高。血清PPARγ、MMP-9及乳酸杆菌三者对急性期MPP具有一定的诊断价值,三者联合具有更高的效能。

关键词: 过氧化物酶体增殖物激活受体, 基质金属蛋白酶9, 支原体肺炎, 肠道菌群

Abstract: Objective To investigate the correlation between the levels of peroxisome proliferator activated receptor (PPARγ) and matrix metalloproteinase-9 (MMP-9) and the intestinal flora of children with mycoplasma pneumoniae pneumonia (MPP) and its diagnostic value. Method A total of 100 children with MPP admitted to Hejian Children's Hospital from January 2021 to January 2023 were collected as the study subjects, according to the course of the disease, they were grouped into an acute phase group (48 cases) and a recovery phase group (52 cases), and 50 healthy children who underwent routine physical examinations in our hospital during the same period were included as the control group, the number of intestinal flora (Escherichia coli, bifidobacteria, Bacteroides, Enterococcus, Lactobacillus) and serum PPARγ, MMP-9 levels were compared among the three groups. Pearson method analysis were applied to analyze the correlation between serum PPARγ, MMP-9 levels and Escherichia coli, bifidobacteria, Bacteroides, Enterococcus, Lactobacillus. Logistic regression was used to analyze the influencing factors of MPP in acute stage and recovery stage. ROC curve was used to analyze the diagnostic value of serum PPARγ, MMP-9 and Lactobacillus levels for acute MPP. Result The numbers of Escherichia coli and Enterococcus and the level of serum MMP-9 in the acute phase group and the recovery phase group were higher than those in the control group, and the acute phase group were higher than that in the recovery phase group (P<0.05); the numbers of Bifidobacterium, Bacteroides, Lactobacillus, and serum PPARγ level in the acute phase group and recovery phase group were lower than those in the control group, and the acute phase group were lower than the recovery phase group (P<0.05). Pearson analysis showed that the numbers of Escherichia coli and Enterococcus were negatively correlated with the serum PPARγ level (P<0.05), there was a positive correlation between the numbers of Bifidobacterium, Bacteroides, and Lactobacillus and the serum PPARγ level (P<0.05); the numbers of Escherichia coli and Enterococcus were positively correlated with the level of serum MMP-9 (P<0.05), there was a negative correlation between the number of Bifidobacterium, Bacteroides, and Lactobacillus and serum MMP-9 level (P<0.05). Logistic regression analysis showed that PPARγ was a protective factor for the development of MPP in acute and recovery stages (P<0.05), MMP-9 was a risk factor for the development of MPP in acute and recovery stages (P<0.05), and Lactobacillus was a protective factor for the development of MPP in acute stage (P<0.05).The AUC of serum PPARγ, MMP-9, Lactobacillus and their combination in the diagnosis of acute MPP were 0.797, 0.761, 0.839 and 0.905, respectively. The sensitivity and specificity of combined diagnosis were 93.24% and 76.34%, respectively. The combination of the three was better than that of serum PPARγ, MMP-9 and Lactobacillus alone (Z Combination of the three-PPARγ=2.604, P<0.001; Z Combination of the three-MMP-9=3.310, P=0.007; Z Combination of the three-Lactobacillus=2.810, P=0.008). Conclusion Serum PPARγ level of MPP children increases with the decreases of Escherichia coli and Enterococcus and the increases of Bifidobacterium, Bacteroides and Lactobacillus, the serum MMP-9 level increases with the increasse of Escherichia coli and Enterococcus and the decreases of bifidobacteria, Bacteroides and Lactobacillus.Serum PPARγ, MMP-9 and Lactobacillus have certain diagnostic value for acute MPP, and the combination of the three has higher efficacy.

Key words: Peroxisome proliferator activated receptor, Matrix metalloproteinase 9, Mycoplasma pneumoniae pneumonia, Intestinal flora

中图分类号:

R725.7

郭建明, 左一宇, 赵爱宝. 血清过氧化物酶体增殖物激活受体和基质金属蛋白酶9水平与支原体肺炎患儿肠道菌群的相关性及其诊断价值[J]. 新发传染病电子杂志, 2023, 8(4): 20-24.

Guo Jianming, Zuo Yiyu, Zhao Aibao. Correlation analysis between intestinal microbiota and serum PPARγ and MMP-9 protein levels in children with Mycoplasma pneumoniae pneumonia and its diagnostic value[J]. Electronic Journal of Emerging Infectious Diseases, 2023, 8(4): 20-24.

参考文献

[1] 蔡辰, 胡培培, 陆敏, 等. 肺泡灌洗液中细胞因子及细胞学水平与重症肺炎支原体肺炎的相关性[J].中华实用儿科临床杂志, 2020, 35(18):1421-1424.
[2] 刘启洁, 何善辉, 唐建军, 等. 急支糖浆联合阿奇霉素治疗小儿支原体肺炎的疗效及对炎症因子水平的影响[J].药物评价研究, 2019, 42(6):1164-1167.
[3] HERNANDEZ-QUILES M, BROEKEMA MF, KALKHOVEN E.PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action[J]. Front Endocrinol, 2021, 12:624112.
[4] KIM S, LEE N, PARK ES, et al.T-Cell Death Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγ-RXRα Heterodimer Formation in Adipogenesis[J]. Mol Cells, 2021,44(1):1-12.
[5] 黄皓, 鲍蕾蕾, 李晓龙, 等. PPARs激动剂对糖尿病伤口的促愈合机制及研究进展[J].实用药物与临床, 2022, 25(12):1127-1131.
[6] 张胜碧, 刘燕玲, 李岚. 地龙提取液对卵清蛋白诱导哮喘小鼠气道重塑及肺组织MMP2、MMP-9、TIMP-1表达的影响[J].中国新药与临床杂志, 2021, 40(7):523-530.
[7] 尹文文, 陈仿群, 汪佳伟. 新生儿肺炎患儿血清心肌酶、C-反应蛋白及基质金属蛋白酶9的变化与病情、感染类型的关系[J].中国妇幼保健, 2020, 35(14):2701-2703.
[8] 胡尧舜, 高广川, 李小容, 等. 肺炎支原体肺炎患儿肠道菌群与血清干扰素-γ和白介素-4水平的关系[J]. 西部医学, 2021, 33(11):1687-1690.
[9] 刘瀚旻, 马融. 儿童肺炎支原体肺炎中西医结合诊治专家共识(2017年制定)[J]. 中国实用儿科杂志, 2017, 32(12):881-885.
[10] 吴琰,魏会平,曹欣,等. 儿童下呼吸道肺炎支原体感染流行特点分析[J/CD]. 新发传染病电子杂志,2021, 6(4):336-338.
[11] AHN JG, CHO HK, LI D, et al.Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis[J]. BMC Infect Dis, 2021, 21(1):1003.
[12] 单鸿伟, 吕政, 肖燕, 等. 危重型新型冠状病毒肺炎有创机械通气患者炎性细胞因子水平的变化分析[J].中华危重病急救医学, 2020, 32(9):1051-1055.
[13] LUO J, WANG J, ZHANG J, et al.Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy-and NF-κB/PPARγ-Mediated Macrophage Polarization[J]. Cells, 2022, 11(23):3927-3948.
[14] 王海利, 韩晓群, 付南燕, 等. 激活PPARγ对结核分枝杆菌感染小鼠肺组织AP-1表达及炎症反应的影响[J].解放军医学杂志, 2022, 47(1):46-52.
[15] 田灵敏. 低分子肝素联合AC治疗IIP患者的疗效分析及其对KL-6、PPARγ水平及肺纤维化相关因子表达的影响[J].包头医学院学报, 2021, 37(9):43-47.
[16] 李菲, 唐萍, 曹蓉. 血清心肌酶、CRP、HMGB1、MMP-9水平在新生儿肺炎感染类型鉴别及病情评估中的应用价值[J].海南医学, 2021, 32(2):164-168.
[17] 段志辉, 程晓伟, 曹友林, 等. 血清NT-proBNP、Copeptin、MMP-9及HMGB1表达水平在重症肺炎患者中的意义[J].热带医学杂志, 2020, 20(6):787-790.
[18] 孙裕平, 于洪波, 张玉英, 等. 血清基质金属蛋白酶-9在中枢神经系统感染患儿中的改变及其与降钙素原、C反应蛋白的相关性分析[J]. 中华急诊医学杂志, 2019, 28(4):525-527.