血浆利钠肽及其活化酶corin在慢性低氧性肺动脉高压患者中的变化及意义探讨

徐平; 罗华; 宋卫东

doi:10.13201/j.issn.1001-1439.2019.05.012

血浆利钠肽及其活化酶corin在慢性低氧性肺动脉高压患者中的变化及意义探讨

- 1. 北京大学深圳医院呼吸内科(广东深圳, 518000);
- 2. 北京大学深圳医院ICU
基金项目:
广东省自然科学基金资助项目（No：2017A030313830）；深圳市卫计委课题资助项目（No：201501021）

详细信息

通讯作者: 徐平,E-mail:799721206@qq.com

中图分类号: R544.1

收稿日期: 2018-12-13

Changes and significances of natriuretic peptide and cardiac protease corin in patients with hypoxic pulmonary hypertension

- 1. Department of Respiratory;
- 2. Intensive Care Unit, Peking University Shenzhen Hospital, Shenzhen, 518000, China

More Information

Corresponding author: XU Ping, E-mail: 799721206@qq.com

Received Date: 13 December 2018

摘要

摘要: 目的：探讨corin与利钠肽在慢性低氧性肺动脉高压发生发展中的临床意义及其对病情的评估作用。方法：纳入慢性低氧性肺动脉高压患者158例，分为2个亚组：轻度肺动脉高压组118例（Ⅰa组）、中重度肺动脉高压组40例（Ⅰb组）；健康对照组60例（Ⅱ组）。ELISA法检测3组患者血浆corin、心房利钠肽（ANP）、脑利钠肽（BNP）、ANP前体（pro-ANP）及BNP前体（pro-BNP）水平，心脏彩色多普勒超声测定肺动脉收缩压（SPAP），血气分析检测动脉血氧分压（PaO₂）。计算pro-ANP/ANP与pro-BNP/BNP比值。采用Spearman检验进行相关性分析。结果：Ⅰa组血浆corin表达水平显著高于Ⅱ组，Ⅰb组较Ⅱ组与Ⅰa组均显著下降（均P<0.01）；Ⅰa组与Ⅰb组血浆ANP、pro-ANP、BNP及pro-BNP均明显高于Ⅱ组，且Ⅰb组显著高于Ⅰa组（均P<0.01）；Ⅰa组pro-ANP/ANP与pro-BNP/BNP均较Ⅱ组显著降低，Ⅰb组较Ⅰa组显著升高（均P<0.01）。相关性分析显示：在Ⅰa组与Ⅰb组中，SPAP与pro-ANP、ANP、pro-BNP、BNP均存在正相关性；在Ⅰa组中，血浆corin与pro-ANP、ANP、pro-BNP、BNP均存在正相关性；而在Ⅰb组中，corin与pro-ANP、ANP、pro-BNP、BNP均存在负相关性。结论：corin与利钠肽及其前体在不同肺动脉高压阶段中表达异常，且二者表达水平具有相关性，提示corin介导利钠肽活化过程，从而参与慢性低氧性肺动脉高压的发生发展。
- corin /
- 利钠肽 /
- 利钠肽前体 /
- 慢性低氧 /
- 肺动脉高压
Abstract: Objective: To explore the clinical significance of corin and natriuretic peptide in the occurrence and development of chronic hypoxic pulmonary hypertension (CHPH).Method: A total of 158 patients with CHPH were enrolled and divided into two subgroups:118 patients with mild CHPH were included into Group Ⅰa, and 40 patients with moderate to severe CHPH were included into Group Ⅰb.Other 60 healthy subjects were enrolled into Group Ⅱ.Levels of plasma corin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ANP precursor (pro-ANP) and BNP precursor (pro-BNP) were measured by ELISA.Pulmonary arterial systolic pressure (SPAP) was measured by color Doppler echocardiography, and arterial partial oxygen pressure (PaO₂) was measured by blood gas analysis.The ratio of pro-ANP/ANP and proBNP/BNP were calculated.Correlation analysis was used by Spearman test.Result: The level of plasma corin in groupⅠa was significantly higher than that in group Ⅱ, and was significantly lower in in groupⅠb than those in group Ⅱ and groupⅠa (all P<0.01).Levels of plasma ANP, pro-ANP, BNP and pro-BNP in groupⅠa and group Ⅰb were significantly higher than those in group Ⅱ, and were significantly higher in group Ⅰb than those in groupⅠa (all P<0.01).pro-ANP/ANP and pro-BNP/BNP in group Ⅰa were significantly lower than those in group Ⅱ, and were significantly higher in group Ⅰb than those in groupⅠa (all P<0.01).The correlation analysis showed that SPAP was positively correlated with pro-ANP, ANP, pro-BNP and BNP in group Ⅰa and group Ⅰb;Plasma corin was positively correlated with pro-ANP, ANP, pro-BNP and BNP in group Ⅰa, but negatively correlated with pro-ANP, ANP, pro-BNP and BNP in group Ⅰb.Conclusion: Corin and natriuretic peptide are abnormally expressed in different stages of pulmonary hypertension, and their expression levels are correlated, suggesting that corin mediates the activation of natriuretic peptideandparticipates in the occurrence and development of CHPH.
- corin /
- natriuretic peptide /
- pro-natriuretic peptide /
- hypoxia /
- pulmonary hypertension

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参考文献(25)

[1]	张卫芳, 葛晓月, 祝田田, 等.缺氧相关性肺动脉高压新靶标:LOX-1[J].临床心血管病杂志, 2018, 34(5):524-527.
[2]	Yan W, Sheng N, Seto M, et al.A mosaic transmembrane serine protease encoded by a novel cDNA from human heart[J].J Biolog Chem, 1999, 274(21):14926-14935.
[3]	Yap LB, Ashrafian H, Mukerjee D, et al.The natriuretic peptides and their role in disorders of right heart dysfunction and pulmonary hypertension[J].Clin Biochem, 2004, 37(10):847-856.
[4]	Nakanishi K, Tajima F, Itoh H, et al.Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats[J].Virchows Arch, 2001, 439(6):808-817.
[5]	Andreassen AK, Wergeland R, Simonsen S, et al.N-terminal pro-B-type natriuretic peptide as an indicator of disease severity in a heterogeneous group of patients with chronic precapillary pulmonary hypertension[J].Am J Cardiol, 2006, 98(4):525-529.
[6]	Chang CL, Robinson SC, Mills GD, et al.Biochemical markers of cardiac dysfunction predict mortality in acute exacerbations of COPD[J].Thorax, 2011, 66(9):764-768.
[7]	McLaughlin VV, Archer SL, Badesch DB, et al.ACCF/AHA 2009 expert consensus document on pulmonary hypertension:a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians;American Thoracic Society, Inc.;and the Pulmonary Hypertension Association[J].J Am Coll Cardiol, 2009, 53(17):1573-1619.
[8]
[9]	Chaouat A, Bugnet AS, Kadaoui N, Schott R, et al.Severe pulmonary hypertension and chronic obstructive pulmonary disease[J].Am J Respir Crit Care Med, 2005, 172(2):189-194.
[10]	Andersen KH, Iversen M, Kjaergaard J, et al.Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease[J].J Heart Lung Transplant, 2012, 31(4):373-380.
[11]	Minai OA, Santacruz JF, Alster JM, et al.McCarthy K.Impact of pulmonary hemodynamics on 6-min walk test in idiopathic pulmonary fibrosis[J].Respir Med, 2012, 106(11):1613-1621.
[12]	Behr J, Ryu JH.Pulmonary hypertension in interstitial lung disease[J].Eur Respir J, 2008, 31(6):1357-1367.
[13]	贾琼, 李强, 徐兆龙.心力衰竭新型药物治疗现状[J].临床心血管病杂志, 2016, 32(7):745-748.
[14]	Nishimura K, Nishimura T, Onishi K, et al.Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis, 2014, 9:155-162.
[15]	Fisher MR, Criner GJ, Fishman AP, et al.Estimating pulmonary artery pressures by echocardiography in patients with emphysema[J].Eur Respir J, 2007, 30(5):914-921.
[16]	Chi SY, Kim EY, Ban HJ, et al.Plasma N-terminal pro-brain natriuretic peptide:a prognostic marker in patients with chronic obstructive pulmonary disease[J].Lung, 2012, 190(3):271-276.
[17]	Corte TJ, Wort SJ, Gatzoulis MA, et al.Elevated brain natriuretic peptide predicts mortality in interstitial lung disease[J].Eur Respir J, 2010, 36(4):819-825.
[18]	Nakanishi K, Tajima F, Itoh H, et al.Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats[J].Virchows ArchVirchows Arch, 2001, 439(6):808-817.
[19]	Mitani Y, Maruyama J, Jiang BH, et al.Atrial natriuretic peptide gene transfection with a novel envelope vector system ameliorates pulmonary hypertension in rats[J].J Thorac Cardiovasc Surg, 2008, 136(1):142-149.
[20]	Klinger JR, Pietras L, Warburton R, et al.Reduced oxygen tension increases atrial natriuretic peptide release from atrial cardiocytes[J].Exp Biol Med, 2001, 226(9):847-853.
[21]	Chen YF, Feng JA, Li P, et al.Atrial natriuretic peptide-dependent modulation of hypoxia-induced pulmonary vascular remodeling[J].Life Sci, 2006, 79(14):1357-1365.
[22]	Khoury EE, Kinaneh S, Aronson D, et al.Natriuretic peptides system in the pulmonary tissue of rats with heart failure:potential involvement in lung edema and inflammation[J].Oncotarget, 2018, 9(31):21715-21730.
[23]	Chen S, Wang H, Li H, et a1.Functional analysis of corin protein domains required for PCSK6-mediated activation[J].Int J Biochem Cell Biol, 2018, 94:31-39.
[24]	Peng J, Jiang J, Wang W, et al.Glycosylation and processing of pro-B-type natriuretic peptide in cardiomyocytes[J].Biochem Biophys Res Commun, 2011, 411(3):593-598.
[25]	Dong N, Chen S, Yang J, et al.Plasma soluble corin in patients with heart failure[J].Circ Heart Fail, 2010, 3(2):207-211.