山东大学耳鼻喉眼学报 ›› 2018, Vol. 32 ›› Issue (2): 43-47.doi: 10.6040/j.issn.1673-3770.0.2017.246

• ·论著· • 上一篇    下一篇

HIF-1α、VEGF在阻塞性睡眠呼吸暂停低通气综合征患者

李浩,李延忠,王岩   

  1. 81170903)第一作者:李浩。E-mail: 353917463@qq.com通讯作者:李延忠。E-mail: liyanzhong@sdu.edu.cnDOI:10.6040/j.issn.1673-3770.0.2017.246·论著·HIF-1α、VEGF在阻塞性睡眠呼吸暂停低通气综合征患者软腭组织中的表达及其意义李浩, 李延忠, 王岩(山东大学齐鲁医院耳鼻咽喉科 国家卫计委耳鼻喉科学重点实验室, 山东 济南 250012
  • 收稿日期:2017-08-04 出版日期:2018-03-20 发布日期:2018-03-20
  • 通讯作者: 李延忠. E-mail: liyanzhong@sdu.edu.cn
  • 基金资助:
    国家自然科学基金项目(81170903)

Hypoxia inducible factor-1 alpha and vascular endothelial growth factor expression in the soft palate of

LI Hao, LI Yanzhong, WANG Yan   

  1. Department of Otolaryngology, Qilu Hospital of Shandong University/Key Laboratory of Otolaryngology, NHFPC(Shandong University), Jinan 250012, Shandong, China
  • Received:2017-08-04 Online:2018-03-20 Published:2018-03-20

摘要: 目的 通过研究阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者软腭组织中HIF-1α、VEGF的表达,探讨HIF-1α、VEGF表达与OSAHS的关系及意义。 方法 选取 30 例 OSAHS 患者作为实验组, 6 例排除OSAHS 的单纯慢性扁桃体炎患者作为对照组。通过HE染色观察软腭组织中肌细胞、血管等的变化, 再通过免疫组化检测软腭组织中 HIF-1α 和 VEGF 的表达。 结果 (1)HE染色结果显示:实验组软腭组织中上皮细胞增生,固有层增厚,肌纤维均存在不同程度的变性,肌纤维排列紊乱,新生毛细血管生成等现象;(2)免疫组化染色结果显示: HIF-1α于OSAHS 中、重度组在黏膜基底层及棘层细胞胞浆高表达,阳性表达主要定位于细胞核和细胞浆呈棕褐色。VEGF在OSAHS 中、 重度组软腭组织黏膜鳞状上皮基底层及棘层细胞胞浆强阳性表达,腺管上皮细胞强阳性表达或局灶强阳性表达,血管内皮细胞部分阳性表达;(3)HIF-1α、VEGF均与 睡眠呼吸暂停低通气指数(AHI)呈正相关(P<0. 05), 与夜间最低氧饱和度呈负相关(P<0. 01)。 结论 OSAHS 患者软腭组织中HIF-1α、 VEGF的表达,与OSAHS严重程度有关, 可能在其发生发展过程中起到重要作用。

关键词: 睡眠呼吸暂停, 阻塞性, 软腭组织, 缺氧诱导因子-1α, 免疫组织化学, 血管内皮生长因子

Abstract: Objective To investigate hypoxia inducible factor-1 alpha(HIF-1α)and vascular endothelial growth factor(VEGF)expression in the soft palate in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS), and to explore the role of these factors in the pathogenesis of OSAHS. Methods Immunohistochemistry was used to detect HIF-1α and VEGF expression in the soft palate of 30 patients with OSAHS(experiment group)and six who had undergone tonsillectomy(control group). Results Hematoxylin-eosin staining of the soft palate revealed epithelial hyperplasia, thickening of the lamina propria, disordered muscle fibers in various stages of degeneration, and angiogenesis in the experimental group. Immunohistochemical staining revealed overexpression of HIF-1α in the nuclei and cytoplasm of cells in the squamous, epithelial, basal, and spinous layers, and strongly positive expression of VEGF in the cytoplasm of cells in the squamous, epithelial, basement, and stratum spinosum layers of the soft palate mucosa in patients with moderate to severe OSAHS. VEGF showed focal positive expression in glandular epithelial cells and vascular endothelial cells. HIF-1α and VEGF expression was positively correlated with the apnea-hypopnea index(P<0.05)and negatively correlated with the lowest nocturnal oxygen saturation(P<0.01). Conclusion Pathologic changes in the soft palate of patients with OSAHS were strongly correlated with the degree of hypoxia. HIF-1α and VEGF may play an important role in the development of OSAHS.

Key words: Soft palate, Hypoxia inducible factor-1 alpha, Vascular endothelial growth factor, Immunohistochemistry, Sleep apnea, obstructive

中图分类号: 

  • R766.7
[1] Arnold J, Sunilkumar M, Krishna V, et al. Obstructive Sleep Apnea[J]. J Pharm Bioallied Sci, 2017, 9(Suppl 1):26-28.
[2] 中华医学会呼吸病学分会睡眠呼吸障碍学组.阻塞性睡眠呼吸暂停低通气综合征诊治指南(2011年修订版)[J]. 中华结核和呼吸杂志,2012(1):9-12.
[3] Himoto T, Fujita K, Nomura T, et al. Roles of Copper in Hepatocarcinogenesis via the Activation of Hypoxia-Inducible Factor-1α[J]. Biol Trace Elem Res, 2016, 174(1):58-64.
[4] Fox SB, Generali D, Berruti A, et al. The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen[J]. Breast Cancer Res, 2011, 13(1):16.
[5] Ku JH, Shin JK, Cho MC, et al. Effect of dutasteride on the expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in rat and human prostate tissue[J]. Scand J Urol Nephrol, 2009, 43(6):445-453.
[6] Davies AL, Desai RA, Bloomfield PS, et al. Neurological deficits caused by tissue hypoxia in neuroinflammatory disease[J]. Ann Neurol, 2013, 74(6):815-825.
[7] Zhou Q, Yang S, Luo Y, et al. A randomly-controlled study on the cardiac function at the early stage of return to the plains after short-term exposure to high altitude[J]. PLoS One, 2012, 7(2):e31097.
[8] Xie M, He CS, Huang JK. Phase II study of pazopanib as second-line treatment after sunitinib in patients with metastatic renal cell carcinoma: a southern china urology cancer consortium trial[J]. Eur J Cancer, 2015, 51(5):595-603.
[9] Manresa MC. Hypoxia Inducible Factor(HIF)Hydroxylases as Regulators of Intestinal Epithelial Barrier Function[J]. Clin Gastroenterol H, 2017, 3(3):303-315.
[10] Schöffski P, Gordon M, Smith DC, et al. Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours[J]. Eur J Cancer, 2017, 86:296-304.
[11] Gieger TL, Nettifee-Osborne J, Hallman B, et al. The impact of carboplatin and toceranib phosphate on serum vascular endothelial growth factor(VEGF)and metalloproteinase-9(MMP-9)levels and survival in canine osteosarcoma[J]. Can J Vet Res, 2017, 81(3):199-205.
[12] Zeng HH, Dong W, Xie YP, et al. Cyclooxygenase-2 overexpression and vascular endothelial growth factor expression in pharyngeal tissue of patients with OSAHS correlates with angiogenesis[J]. Chin J Physiol, 2011, 27(2):210-213.
[13] Salord N, Gasa M, Mayos M, et al. Impact of OSA on biological markers in morbid obesity and metabolic syndrome[J]. J Clin Sleep Med, 2014, 10(3):263-270.
[14] Joy NG, Mikeladze M, Younk LM, et al. Effects of equivalent sympathetic activation during hypoglycemia on endothelial function and pro-atherothrombotic balance in healthy individuals and obese standard treated type 2 diabetes[J]. Metabolism, 2016, 65(12):1695-1705.
[15] Archontogeorgis K, Nena E, Papanas N, et al. Serum levels of vascular endothelial growth factor and insulin-like growth factor binding protein-3 in obstructive sleep apnea patients: effect of continuous positive airway pressure treatment[J]. J Cardiovasc Med, 2015, 9:133-138.
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