脓毒症早期BMP-2和BMP-4的变化

doi:10.16352/j.issn.1001-6325.2022.04.020

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (4): 628-632.doi: 10.16352/j.issn.1001-6325.2022.04.020

脓毒症早期BMP-2和BMP-4的变化

温燕¹, 林金灿², 黄颖泓¹, 肖文彪¹, 张民伟², 林建东^1*

1.福建医科大学附属第一医院重症医学科, 福建福州 350005;
2.厦门大学附属第一医院重症医学科,福建厦门 361003

收稿日期:2021-06-28 修回日期:2021-12-13 出版日期:2022-04-05 发布日期:2022-04-01
通讯作者: * linjdfyyy@outlook.com
基金资助:
中华医学会临床医学科研专项资金-国瑞重症科研项目(13091440529)

Changes of BMP-2 and BMP-4 in early phase of sepsis

WEN Yan¹, LIN Jin-can², HUANG Ying-hong¹, XIAO Wen-biao¹, ZHANG Min-wei², LIN Jian-dong^1*

1. Department of Intensive Care Unit, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005;
2. Department of Intensive Care Unit, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China

Received:2021-06-28 Revised:2021-12-13 Online:2022-04-05 Published:2022-04-01
Contact: * linjdfyyy@outlook.com

摘要/Abstract

摘要： 目的探讨骨形态发生蛋白-2(BMP-2)和骨形态发生蛋白-4(BMP-4)在脓毒症发病中的变化规律及作用机制。方法收集入住重症医学科(ICU)24 h内的脓毒症患者(脓毒症组)、非脓毒症患者(非脓毒症组)和健康志愿者(对照组)的血清,ELISA测定血清BMP-2和BMP-4浓度。免疫印迹法检测经脂多糖(LPS)处理后的大鼠肺微血管内皮细胞(PMECs)的BMP-2、磷酸化Smad(pSmad)1/5和BMP受体Ⅱ(BMPRⅡ)的表达。结果脓毒症患者血清 BMP-2和BMP-4水平显著较高(P＜0.05);脓毒症组 BMP-2水平显著高于非脓毒症组(P＜0.05)。BMP-2在脓毒症和健康志愿者间及脓毒症和非脓毒症组间有较好的诊断价值。LPS可显著升高PMECs的BMP-2表达量,而降低pSmad1/5和BMPRⅡ的表达量(P＜0.05)。结论 BMP-2可能是脓毒症早期潜在的诊断标志物,并作为促炎因子起作用。

关键词: 脓毒症, BMP-2, BMP/pSmad, 肺微血管上皮细胞

Abstract: Objective To study the change of serum bone morphogenetic protein (BMP)-2 and BMP-4 during the development of sepsis and its mechanisms. Methods Blood was collected for quantifying serum BMP-2 and BMP-4 from patients with sepsis (sepsis group), patients without sepsis (non-sepsis group) in 24 hours of ICU admission and from healthy volunteers (control group). Concentration of serum BMP-2 and BMP-4 was determined by ELISA. The expression of BMP-2, pSmad1/5, and BMPRⅡ of lip polysaccharide (LPS)-treated rat pulmonary microvascular endothelial cells (RPMECs) was detected by Western blot. Results Serum BMP-2 and BMP-4 were significantly increased in sepsis group (P＜0.05) and the level of BMP-2 was significantly higher in sepsis group than that in non-sepsis group (P＜0.05). BMP-2 was found to be a marker for differential diagnosis of separating sepsis LPS may significantly increase the expression of BMP-2 of RPMECs but decrease the expression of phosphorylated Smad1/5 (pSmad1/5) and BMP receptor Ⅱ (BMPRⅡ) (P＜0.05). Conclusions BMP-2 is a potential diagnostic marker and act as apro-inflammatory factor in early phase of sepsis.

Key words: sepsis, BMP-2, BMP/pSmad, pulmonary microvascular endothelial cells

中图分类号:

温燕, 林金灿, 黄颖泓, 肖文彪, 张民伟, 林建东. 脓毒症早期BMP-2和BMP-4的变化[J]. 基础医学与临床, 2022, 42(4): 628-632.

WEN Yan, LIN Jin-can, HUANG Ying-hong, XIAO Wen-biao, ZHANG Min-wei, LIN Jian-dong. Changes of BMP-2 and BMP-4 in early phase of sepsis[J]. Basic & Clinical Medicine, 2022, 42(4): 628-632.

参考文献

[1] Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016[J]. Crit Care Med, 2017, 45:486-552.
[2] Evans T. Diagnosis and management of sepsis[J]. Clin Med (Lond), 2018, 18:146-149.
[3] Finkenzeller G, Hager S, Stark GB. Effects of bone morphogenetic protein 2 on human umbilical vein endothelial cells[J]. Microvasc Res, 2012, 84:81-85.
[4] Yao Y, Watson AD, Ji S, et al. Heat shock protein 70 enhances vascular bone morphogenetic protein-4 signaling by binding matrix Gla protein[J]. Circ Res, 2009, 105:575-584.
[5] Csiszar A, Lehoux S, Ungvari Z. Hemodynamic forces, vascular oxidative stress, and regulation of BMP-2/4 expression[J]. Antioxid Redox Signal, 2009, 11:1683-1697.
[6] Csiszar A, Labinskyy N, Jo H, et al. Differential proinflammatory and prooxidant effects of bone morphogenetic protein-4 in coronary and pulmonary arterial endothelial cells[J]. Am J Physiol Heart Circ Physiol, 2008, 295:H569-H577.
[7] Helbing T, Rothweiler R, Ketterer E, et al. BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium[J]. Blood, 2011, 118:5040-5049.
[8] Chen QH, Liu AR, Qiu HB, et al. Interaction between mesenchymal stem cells and endothelial cells restores endothelial permeability via paracrine hepatocyte growth factor in vitro[J]. Stem Cell Res Ther, 2015, 6:44.doi:10.1186/s13287-015-0025-1.
[9] Akahori H, Tsujino T, Masuyama T, et al. Mechanisms of aortic stenosis[J]. J Cardiol,2018, 71:215-220.
[10] Hanna A, Frangogiannis NG. The role of the TGF-β superfamily in myocardial infarction[J]. Front Cardiovasc Med, 2019, 6:140.doi:10.3389/fcvm.2019.00140.
[11] Sánchez-Duffhues G, García de Vinuesa A, van de Pol V, et al. Inflammation induces endothelial-to-mesenchymal transition and promotes vascular calcification through downregulation of BMPR2[J]. J Pathol, 2019, 247:333-346.
[12] Kim CW, Song H, Kumar S, et al. Anti-inflammatory and antiatherogenic role of BMP receptor Ⅱ in endothelial cells[J]. Arterioscler Thromb Vasc Biol, 2013, 33:1350-1359.
[13] 庞新岗,李永刚,包倪荣,等. 骨代谢主要信号通路及信号分子的研究进展[J]. 基础医学与临床, 2018, 38: 1799-1803.

脓毒症早期BMP-2和BMP-4的变化

Changes of BMP-2 and BMP-4 in early phase of sepsis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 7

编辑推荐

Metrics

本文评价

[1]	林柏柏, 钱风华, 钱义明, 赵雷, 孙旗, 褚梦瑶, 沈梦雯. 脓毒症并发毛细血管渗漏综合征的研究进展[J]. 基础医学与临床, 2022, 42(7): 1144-1147.
[2]	王玉龙滕文彬单跃姚刘旭何锐李玉红祝胜美. HIF-1α激动或拮抗剂对脓毒症大鼠肠道黏膜通透性的影响[J]. 基础医学与临床, 2021, 41(11): 1618-1623.
[3]	邵瑞飞, 杨艳, 郑志榕, 赵世民, 陈国兵. 肠道菌群和“肠-肺”轴在脓毒症中的作用[J]. 基础医学与临床, 2020, 40(8): 1109-1112.
[4]	何锐朱烨柯滕文彬单跃易声华祝胜美李玉红. 甘油可能通过水通道蛋白3减轻脓毒症小鼠肠黏膜屏障损伤[J]. 基础医学与临床, 2020, 40(5): 655-661.
[5]	文大林杜娟陈民佳孙剑会张华才张安强都定元. 联合检测C反应蛋白和降钙素原在创伤后脓毒症患者早期预警中的作用[J]. 基础医学与临床, 2020, 40(2): 178-181.
[6]	吴铭蒋苇苇高莉莉. 脂氧素A4降低LPS致肥胖大鼠炎性因子的释放[J]. 基础医学与临床, 2018, 38(12): 1749-1752.
[7]	王瑞兰魏乔康福新曹戍李国平茹松伟李彩花. 眼镜蛇毒因子抑制脓毒症大鼠的炎症反应[J]. 基础医学与临床, 2008, 28(11): 1178-1182.