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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2017年第4期

页码:

399-404

栏目:

基础研究

出版日期:

2017-02-25

文章信息/Info

Title:

CTRP9 inhibits expressions of IL-6 and TNF-α in pulmonary microvascular endothelial cell under hypoxia condition

作者:

金巧艳¹; 曾明华¹; 谭延振²; 苏 慧³; 易 蔚²; 张海锋⁴; 孙 新¹

第四军医大学：1.西京医院儿科，2.西京医院心血管外科，3.西京医院老年病科，4.教学实验中心，陕西 西安 710032

Author(s):

JIN Qiao-yan¹;  ZENG Ming-hua¹;  TAN Yan-zhen²;  SU Hui³;  YI Wei²;  ZHANG Hai-feng⁴;  SUN Xin¹

1.Department of Pediatrics, 2.Department of Cardiovascular Surgery, 3.Department of Geriatrics, Xijing Hospital, 4.Experiment Teaching Center, Fourth Military Medical University, Xi’an 710032, Shaanxi, China

关键词:

C1q肿瘤坏死因子相关蛋白9; 低氧性肺动脉高压; 肺微血管内皮细胞; 白介素-6; 肿瘤坏死因子-α

Keywords:

CTRP9;  Hypoxic pulmonary hypertension;  pulmonary microvascular endothelial cell;  Interleukin-6;  Tumor necrosis factor alpha

分类号:

R543.2

DOI:

-

文献标识码:

A

摘要:

目的 研究低氧环境下C1q肿瘤坏死因子相关蛋白9（C1q/TNF-related protein 9，CTRP9）对肺微血管内皮细胞（Pulmonary microvascular endothelial cell，PMVEC）中白介素(IL)-6、肿瘤坏死因子(TNF)-α表达的影响。方法 将雄性SD大鼠随机分为常氧组、低氧组，采用低压低氧法建立大鼠低氧性肺动脉高压（Hypoxic pulmonary hypertension，HPH）模型，28 d后检测各组大鼠血流动力学、右心室肥厚指标和组织病理学改变；用RT-PCR检测HPH大鼠肺组织中IL-6、TNF-α mRNA表达水平；用ELISA法检测二者在血清中的变化。分离培养健康雄性SD大鼠的PMVEC，分别在常氧（210 ml/L O2、50 ml/L CO2）、低氧（50 ml/L O2、50 ml/L CO2）、或者低氧+CTRP9（5 μg/ml）环境中孵育48 h。结果 与常氧组相比，低氧组大鼠右心室收缩压和右心室肥厚指标增加（P<0.05），肺小动脉管壁增厚，显示造模成功；肺组织中IL-6、TNF-α mRNA水平上调（P<0.05），两种炎症因子在血清中的含量增加（P<0.05）。与常氧组相比，低氧处理使两种炎症因子IL-6、TNF-α在PMVEC中mRNA水平及在细胞培养上清中的含量均增加（P<0.05）；在低氧的同时给予CTRP9孵育时，与单纯低氧组相比，两种炎症因子在PMVEC中mRNA水平及在细胞培养上清中的含量均降低（P<0.05）。结论 大鼠发生HPH时，炎症因子IL-6、TNF-α表达升高。而CTRP9对低氧条件下PMVEC表达和分泌IL-6及TNF-α具有抑制作用，进而有望预防或延缓HPH的发生发展。

Abstract:

AIM To investigate the effects of CTRP9 on hypoxia-induced expressions of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in pulmonary microvascular endothelial cells (PMVECs). METHODS SD rats were randomly divided into normoxic group and hypoxic group. The rats in the hypoxic group were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin (air pressure 55 kPa, oxygen concentration 10%) for 28 days to establish the animal model of hypoxic pulmonary hypertension (HPH). The histopathological change, the hemodynamic index and the right ventricular hypertrophy index of rats were detected. The mRNA levels of IL-6 and TNF-α in lungs were determined by RT-PCR and serum IL-6 and TNF-α were measured by ELISA. Primary PMVEC were cultured under normoxia, hypoxia (50 ml/L O2) or hypoxia with CTPR9 treatment and mRNA of IL-6 and TNF-α in the cell lysate was determined by RT-PCR. RESULTS In the hypoxia group, the right ventricular systolic pressure, the right ventricular hypertrophy index and the thickness of pulmonary arterial wall were increased compared with those in the normoxia group（P<0.05）. The expressions of IL-6 and TNF-α in PMVEC increased significantly under hypoxia environment（P<0.05） and CTRP9 treatment effectively inhibited the increase（P<0.05）. CONCLUSION SThe expressions of IL-6 and TNF-α increase in HPH rats. CTRP9 could effectively inhibit the expressions and secretions of inflammatory cytokines IL-6 and TNF-α in PMVEC in hypoxia condition, which makes CTRP9 a potential therapy to prevent and limit the development of HPH.

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备注/Memo

备注/Memo:

收稿日期：2016-10-28.基金项目：国家自然科学基金资助（81670449,31371151，31271219）； 陕西省国际合作课题项目资助（2013KW30-02） 通讯作者：孙新，副教授，主要从事肺动脉高压研究 Email:sunxin6@fmmu.edu.cn 共同通讯作者：张海锋，副教授，主要从事心血管保护的研究 Email:hfzhang@fmmu.edu.cn 作者简介：金巧艳，硕士生Email:qiaoyanjin@126.com

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