支气管哮喘患者外周血蛋白磷酸酶1A水平与气道重塑的关系

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摘要目的探讨支气管哮喘患者外周血蛋白磷酸酶1A（PPM1A）水平与气道重塑的关系。方法选择2017年8月至2020年1月广东省中山市博爱医院（以下简称“我院”）收治的114例支气管哮喘患者，参考全球哮喘倡议中哮喘分级标准将患者分为重度组（51例）和轻中度组（63例），另选择我院同期50名健康志愿者为对照组。检测血清PPM1A、白细胞介素（IL）-4、IL-17A、IL-13水平，肺功能和气道重塑指标。分析血清PPM1A水平与气道重塑、肺功能、IL-4、IL-17A、IL-13相关性。结果重度组和轻中度组血清PPM1A水平、第1秒用力呼气容积（FEV1）、FEV1与用力肺活量的比值（FEV1/FVC）、FEV1占预计值百分数（FEV1%pred）低于对照组，重度组血清PPM1A水平、FEV1、FEV1/FVC、FEV1%pred低于轻中度组，差异有统计学意义（P ＜ 0.05）。重度组和轻中度组IL-17A、IL-13、IL-4水平，气道壁厚度/气道外径百分比、气道壁面积占气道总面积百分比高于对照组，重度组IL-17A、IL-13、IL-4水平，气道壁厚度/气道外径百分比、气道壁面积占气道总面积百分比高于轻中度组，差异有统计学意义（P ＜ 0.05）。线性回归方程为PPM1A=2.035+0.492 IL-4-0.671 IL-17A -0.503 IL-13+0.586 FEV1+0.416 FEV1/FVC +0.356 FEV1%pred -0.725气道壁厚度/气道外径百分比-0.783气道壁面积占气道总面积百分比（R2 = 0.786，调整后R2 = 0.753，F = 39.265，P ＜ 0.001），支气管哮喘患者PPM1A水平与FEV1、FEV1/FVC、FEV1%pred呈正相关（P ＜ 0.05），与气道壁厚度/气道外径百分比、气道壁面积占气道总面积百分比、IL-4、IL-17A、IL-13呈负相关（P ＜ 0.05）。结论支气管哮喘患者外周血PPM1A水平明显下降，PPM1A缺失可能参与了支气管哮喘气道重塑过程。

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	徐蕾1 贺新华1 陈昂2 谭宪3

关键词 ：支气管哮喘, 蛋白磷酸酶1A, 气道重塑, 转化生长因子 &beta, 肺功能

Abstract：Objective To investigate the relationship between peripheral blood protein phosphatase magnesium-dependent 1A (PPM1A) level and airway remodeling in patients with bronchial asthma. Methods A total of 114 patients with bronchial asthma admitted to Boai Hospital of Zhongshan, Guangdong Province (hereinafter referred to as “our hospital”) from August 2017 to January 2020 were selected. The patients were divided into severe group (51 cases) and mild to moderate group (63 cases) according to the asthma grading standards in the Global Asthma Initiative. Another 50 healthy volunteers from our hospital during the same period were selected as the control group. Serum levels of PPM1A, interleukin (IL)-4, IL-17A, IL-13, lung function and airway remodeling were measured. The correlation between serum PPM1A level and airway remodeling, lung function, IL-4, IL-17A, and IL-13 was analyzed. Results Serum PPM1A level, forced expiratory volume in one second (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and percentage of FEV1 to predicted value (FEV1%pred) in severe and mild to moderate groups were lower than those in the control group, the levels of serum PPM1A, FEV1, FEV1/FVC, and FEV1%pred in severe group were lower than those in mild to moderate group, with statistical significance (P < 0.05). The levels of IL-17A, IL-13, and IL-4, the percentage of airway wall thickness/airway outer diameter and the percentage of airway wall area/total area of the airway in the severe and mild to moderate groups were higher than those in the control group. The levels of IL-17A, IL-13 and IL-4, the percentage of airway wall thickness/airway outer diameter to the percentage of airway wall area/total area of the airway in the severe group were higher than those in the mild to moderate group, and the differences were statistically significant (P < 0.05). The linear regression equation was PPM1A=2.035+0.492 IL-4-0.671 IL-17A -0.503 IL-13+0.586 FEV1+0.416 FEV1/FVC +0.356 FEV1%pred -0.725 percentage of airway wall thickness/airway outer diameter-0.783 percentage of airway wall area/total area of the airway（R2 = 0.786，adjustment R2 = 0.753，F = 39.265，P ＜ 0.001）. The level of PPM1A in asthmatic patients was positively correlated with FEV1, FEV1/FVC and FEV1%pred (P < 0.05), and negatively correlated with the percentage of airway wall thickness/airway outer diameter, the percentage of airway wall area/total area of the airway, IL-4, IL-17A, and IL-13 (P < 0.05). Conclusion The level of PPM1A in peripheral blood of patients with bronchial asthma decreased significantly, and the loss of PPM1A may be involved in the process of airway remodeling in bronchial asthma.

Key words： Bronchial asthma Protein phosphatase magnesium-dependent 1A Airway remodeling Transforming growth factor β Lung function

基金资助:广东省自筹经费类科技计划项目（2017ZC0511）；
广东省中山市社会公益科技研究项目（2018B1103）。

作者简介: 徐蕾（1969.3-），女，副主任医师；研究方向：呼吸内科。

引用本文:

徐蕾1 贺新华1 陈昂2 谭宪3. 支气管哮喘患者外周血蛋白磷酸酶1A水平与气道重塑的关系[J]. 中国医药导报, 2021, 18(25): 98-102.
XU Lei1 HE Xinhua1 CHEN Ang2 TAN Xian3. Relationship between peripheral blood protein phosphatase magnesium-dependent 1A level and airway remodeling in patients with bronchial asthma. 中国医药导报, 2021, 18(25): 98-102.

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https://www.yiyaodaobao.com.cn/CN/ 或 https://www.yiyaodaobao.com.cn/CN/Y2021/V18/I25/98

[1] Bergmann KC. Bronchial asthma - many types，different therapies [J]. Dtsch Med Wochenschr，2016，141（10）：687-692.
[2] Hur GY，Broide DH. Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma [J]. Allergy Asthma Immunol Res，2019，11（5）：604-621.
[3] 史雅旭，戴曦，王丽娇，等.川芎嗪调节TGF-β/Smad信号通路对哮喘小鼠气道炎症和气道重塑的影响[J].现代药物与临床，2019，34（1）：20-26.
[4] Lin X，Duan X，Liang YY，et al. PPM1A Functions as a Smad Phosphatase to Terminate TGFbeta Signaling [J]. Cell，2016，166（6）：1597.
[5] 中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南（2016年版）[J].中华结核和呼吸杂志，2016，39（9）：675-697.
[6] Boulet LP，FitzGerald JM，Levy ML，et al. A guide to the translation of the Global Initiative for Asthma（GINA）strategy into improved care [J]. Eur Respir J，2012，39（5）：1220-1229.
[7] 华雯，黄华琼，沈华浩，等.《支气管哮喘防治指南（2016年版）》解读[J].浙江大学学报：医学版，2016，45（5）：447-452.
[8] Hu L，Li L，Zhang H，et al. Inhibition of airway remodeling and inflammatory response by Icariin in asthma [J]. BMC Complement Altern Med，2019，19（1）：316.
[9] 吴迪，杨勤军，李泽庚，等.支气管哮喘气道重塑发生机制及其中西医防治现状[J].辽宁中医药大学学报，2019， 21（5）：105-108.
[10] Robinson D，Humbert M，Buhl R，et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma：current knowledge and therapeutic implications [J]. Clin Exp Allergy，2017，47（2）：161-175.
[11] 王聪慧.趋化因子CXCL13在支气管哮喘中的作用研究[D].合肥：安徽医科大学，2017.
[12] 李鑫，刘圆圆，张才擎.IL-27通过PI3K/Akt通路对哮喘小鼠气道重塑的影响[J].中国药理学通报，2020，36（6）：798-803.
[13] 周亚莉，胡文君，高尧颖，等.蛋白磷酸酶PPMIA的研究进展[J].生理科学进展，2018，49（5）：363-366.
[14] Gao YD，Zheng JW，Li P，et al. Store-operated Ca2+entry is involved in transforming growth factor-β1 facilitated proliferation of rat airway smooth muscle cells [J]. JAsthma，2013，50（5）：439-448.
[15] Jeon WY，Shin IS，Shin HK，et al. Aqueous extract of gumiganghwal-tang，a traditional herbal medicine，reduces pulmonary fibrosis by transforming growth factor-beta1/smad signaling pathway in murine model of chronic asthma [J]. PLoS One，2016；11（10）：e0164833.
[16] Ojiaku CA，Chung E，Parikh V，et al. TGF-beta1 decreases beta2-agonist-induced relaxation in human airway smooth muscle [J]. Am J Respir Cell Mol Biol，2019， 61（2）：209-218.
[17] Zhang J，Han C，Song K，et al. The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads，SETD2 and PPM1A in hepatic cells [J]. PLoS One，2020，15（1）：e0228160.
[18] Duan X，Liang YY，Feng XH，et al. Protein serine/threonine phosphatase PPMIA dephosphorylates Smad1 in the bone morphogenetic protein signaling pathway [J]. J Biol Chem，2006，281（48）：36526-36532.
[19] Dai F，Shen T，Li L，et al. PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3 [J]. EMBO Rep，2011，12（11）：1175-1181.
[20] Zhou J，Lan Q，Li W，et al. Tripartite motif protein 52（TRIM52）promoted fibrosis in LX-2 cells through PPM1A-mediated Smad2/3 pathway [J]. Cell Biol Int，2019.
[21] Cho O，Oh YT，Chun M，et al. Prognostic implication of FEV1/FVC ratio for limited-stage small cell lung cancer [J]. J Thorac Dis，2018，10（3）：1797-1805.
[22] 徐香琴.CXCL12/CXCR4生物学轴是否会促进哮喘气道上皮细胞分泌MMP9[D].武汉：华中科技大学，2013.
[23] 张筱骞.支气管哮喘患者血清TSLP、C3a和MMP-9水平测定及临床价值探讨[J].中国现代医生，2020，58（19）：43-46.
[24] 汪婷，程真顺，刘媛，等.TGF-β1/Smad2通路参与IL-17诱导的A549细胞上皮-间质转化[J].武汉大学学报：医学版，2017，38（5）：720-723.
[25] 陈秋仪，任培中，王佳美，等.加减乌梅丸颗粒对哮喘大鼠激素干预模型气道重塑及转化生长因子-β_1/Smad信号通路的影响[J].世界中医药，2020，15（8）：1114-1119.
[26] 孟祥珍.合应用IL-4MT及sIL-5Rα对哮喘小鼠气道重塑及TGF-β1、Act-A的影响[D].西安：第四军医大学，2015.