低氧对人肺动脉平滑肌和人肺动脉内皮细胞中HMGB1及相关炎症因子表达的影响*

doi:10.12047/j.cjap.5746.2019.088

中国应用生理学杂志 ›› 2019, Vol. 35 ›› Issue (5): 406-409.doi: 10.12047/j.cjap.5746.2019.088

低氧对人肺动脉平滑肌和人肺动脉内皮细胞中HMGB1及相关炎症因子表达的影响^*

卜宝英¹, 徐喜媛^1Δ, 韩俊萍², 杨敬平¹

1. 内蒙古医科大学第三附属医院呼吸与危重症医学科, 包头 014010;
2. 邯郸第一医院, 河北邯郸 056000

收稿日期:2018-09-07 出版日期:2019-09-28 发布日期:2020-01-02
通讯作者: ^△Tel: 15540869847; E-mail: xuxiyuan9@sina.com
基金资助:
内蒙古医科大学百万工程 (YKD2014JBW016)

Effects of hypoxia on the expression of HMGB1 and related inflammatory factors in human pulmonary artery smooth muscle and pulmonary artery endothelial cells

BU Bao-ying¹, XU Xi-yuan^1Δ, HAN Jun-ping², YANG Jing-ping¹

1. Department of Respiratory and Critical Medicine, the Third Affiliated Hospital, Inner Mongolia Medical University, Baotou 014010;
2. The First Hospital of Handan, Handan 056000, China

Received:2018-09-07 Online:2019-09-28 Published:2020-01-02

摘要/Abstract

摘要： 目的:探讨低氧时人肺动脉平滑肌细胞(HPASMC)和人肺动脉内皮细胞(HPAEC)的高迁移率族蛋白1(HMGB1)及相关受体和炎症因子表达,并检测HMGB1对两种细胞增殖、迁移活性的影响。方法:低氧(1%氧浓度,Hypoxia组)及常氧(Control组)条件下培养HPASMC和HPAEC,RealTime-PCR检测两种细胞HMGB1、TLR2、TLR4、TLR9、RAGE、CD24、IL-6 、TNF-a和CXCL8 mRNA等受体和炎性因子的表达。MTS法观察不同浓度HMGB1对HPASMC和HPAEC增殖的影响;划痕法观察HMGB1对HPASMC和HPAEC迁移的影响。结果:Hypoxia组HPASMC、HPAEC中HMGB1及RAGE mRNA表达量较Control 组明显升高(P＜0.05及0.01);Hypoxia组HPAEC中CD24及HPASMC中IL-6 mRNA表达明显增高(P均＜0.05)。MTS结果显示在345 pmol/L 剂量下 HMGB1明显抑制HPAEC的增殖(P＜0.01),而对HPASMC增殖无影响。划痕实验示HMGB1对HPASMC和HPAEC迁移无明显影响。结论:低氧诱导HPAEC、HPASMC 产生HMGB1;HMGB1通过抑制HPAEC增殖引起内皮屏障功能障碍;而低氧进一步刺激HPASMC产生炎症因子。

关键词: 高迁移率族蛋白1, 低氧, 人肺动脉平滑肌细胞, 人肺动脉内皮细胞, 大鼠

Abstract: Objective: To investigate the effects of hypoxia on the expressions of high mobility group box-1(HMGB1), HMGB1 receptors and inflammatory factors in human pulmonary artery smooth muscle cell( HPASMC) and human pulmonary artery endothelial cells (HPAEC).The effects of HMGB1 on the proliferation and migration activity of the two kinds of cells were detected. Methods: HPASMC and HPAEC were cultured under hypoxic conditions (Hypoxia at 1% oxygen, Hypoxia group) and normoxic conditions(Control group) . The mRNA levels of HMGB1, Toll-like receptors 2,4,9 (TLR2 , TLR4, TLR9), the receptor of advanced glycation end products(RAGE) , CD24 and IL-6 ,TNF-α,CXCL8 were detected by real-time PCR. Cell proliferation was measured by MTS. Cell migration was analysed by wound healing test. Results: Compared with control group, the expressions of HMGB1 mRNA and RAGE mRNA in both HPASMC and HPAEC were increased significantly (P＜0.05 and 0.01). Meanwhile, the expressions of CD24 mRNA in HPAEC and IL-6 mRNA in HPASMC of hypoxia group were increased significantly (P＜0.05). MTS results showed that HMGB1 inhibited the proliferation of HPAEC at 345 pmol/L significantly (P＜0.01). HMGB1 had no effect on the proliferation of HPASMC. Wound healing test showed that HMGB1 had no significant effect on HPASMC and HPAEC. Conclusion: HMGB1 was produced by HPAEC and HPASMC induced by hypoxia. HMGB1 induces endothelial barrier dysfunction by inhibiting HPAEC proliferation. Hypoxia stimulates HPASMC to produce inflammatory cytokines.

Key words: hypoxia, high-mobility group box 1, human pulmonary artery endothelial cells, human pulmonary artery smooth muscle cells, rat

卜宝英, 徐喜媛, 韩俊萍, 杨敬平. 低氧对人肺动脉平滑肌和人肺动脉内皮细胞中HMGB1及相关炎症因子表达的影响^*[J]. 中国应用生理学杂志, 2019, 35(5): 406-409.

BU Bao-ying, XU Xi-yuan, HAN Jun-ping, YANG Jing-ping. Effects of hypoxia on the expression of HMGB1 and related inflammatory factors in human pulmonary artery smooth muscle and pulmonary artery endothelial cells[J]. CJAP, 2019, 35(5): 406-409.

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低氧对人肺动脉平滑肌和人肺动脉内皮细胞中HMGB1及相关炎症因子表达的影响^*

Effects of hypoxia on the expression of HMGB1 and related inflammatory factors in human pulmonary artery smooth muscle and pulmonary artery endothelial cells

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