山东大学耳鼻喉眼学报 ›› 2021, Vol. 35 ›› Issue (5): 93-97.doi: 10.6040/j.issn.1673-3770.0.2020.466
樊慧娟1,张海利2
FAN Huijuan1,ZHANG Haili2
摘要: 中耳胆脂瘤是一种主要由角蛋白碎片和角化鳞状上皮及其周围的结缔组织组成的具有侵袭性的疾病,受很多因素影响,发病机制不明确。随着科学技术的进步,研究学者开始从分子生物学方面研究中耳胆脂瘤的发病机制,其中缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF)具有多种生物学功能,在中耳胆脂瘤的发病机制中可能有着重要作用。本文主要综述HIF-1α和VEGF的生物学特性,以及两者在中耳胆脂瘤的增殖、凋亡、免疫反应及侵蚀性生长等方面可能的作用,从而为了解HIF-1α和VEGF在胆脂瘤的发病机制中的作用和中耳胆脂瘤的非手术治疗、药物研发提供可能。
中图分类号:
| [1] Yung M, Tono T, Olszewska E, et al. EAONO/JOS joint consensus statements on the definitions, classification and staging of middle ear cholesteatoma[J]. J Int Adv Otol, 2017, 13(1): 1-8. doi:10.5152/iao.2017.3363. [2] Kuo CL. Etiopathogenesis of acquired cholesteatoma: prominent theories and recent advances in biomolecular research[J]. Laryngoscope, 2015, 125(1): 234-240. doi:10.1002/lary.24890. [3] Hamed MA, Nakata S, Shiogama K, et al. Cytokeratin 13, cytokeratin 17, and ki-67 expression in human acquired cholesteatoma and their correlation with its destructive capacity[J]. Clin Exp Otorhinolaryngol, 2017, 10(3): 213-220. doi:10.21053/ceo.2016.01263. [4] 宋少鹏, 李文文, 马秀岚. 细胞凋亡在后天性中耳胆脂瘤发病机制中的研究进展[J]. 临床耳鼻咽喉头颈外科杂志, 2019, 33(6): 572-576. doi:10.13201/j.issn.1001-1781.2019.06.025. SONG Shaopeng, LI Wenwen, MA Xiulan. Advances in research on apoptosis in the pathogenesis of acquired middle ear cholesteatoma[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2019, 33(6): 572-576. doi:10.13201/j.issn.1001-1781.2019.06.025. [5] 宋晓宇, 宋西成. 缺氧诱导因子-1α在甲状腺癌中的调节机制[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 136-138, 148. doi:10.6040/j.issn.1673-3770.0.2018.317. SONG Xiaoyu, SONG Xicheng. Research progress on the regulation of HIF-1α expression in thyroid carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 136-138, 148. doi:10.6040/j.issn.1673-3770.0.2018.317. [6] 李浩, 李延忠, 王岩. 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[J]. 山东大学耳鼻喉眼学报, 2018, 32(2): 43-47. doi:10.6040/j.issn.1673-3770.0.2017.246. LI Hao, LI Yanzhong, WANG Yan. Hypoxia inducible factor-1 alpha and vascular endothelial growth factor expression in the soft palate of patients with obstructive sleep apnea hypopnea syndrome[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(2): 43-47. doi:10.6040/j.issn.1673-3770.0.2017.246. [7] Shih CP, Lee JT, Chen HK, et al. Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia[J].Sci Rep, 2018, 8(1): 125. doi:10.1038/s41598-017-18536-y. [8] Koyasu S, Kobayashi M, Goto Y, et al. Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge[J]. Cancer Sci, 2018, 109(3): 560-571. doi:10.1111/cas.13483. [9] Hirota K. Basic biology of hypoxic responses mediated by the transcription factor HIFs and its implication for medicine[J]. Biomedicines, 2020, 8(2): E32. doi:10.3390/biomedicines8020032. [10] Semenza GL. HIF-1 and human disease: one highly involved factor[J]. Genes Dev, 2000, 14(16): 1983-1991. [11] Ke Q, Costa M. Hypoxia-inducible factor-1(HIF-1)[J]. Mol Pharmacol, 2006,70(5):1469-1480. doi: 10.1124/mol.106.027029. [12] Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy[J]. Nat Rev Drug Discov, 2016, 15(6): 385-403. doi:10.1038/nrd.2015.17. [13] Melincovici CS, Bo??塂ca AB, ??塁u??塂man S, et al. Vascular endothelial growth factor(VEGF)-key factor in normal and pathological angiogenesis[J]. Revue Roumaine De Morphol et Embryol, 2018, 59(2): 455-467. [14] Smith GA, Fearnley GW, Harrison MA, et al. Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease[J]. J Inherit Metab Dis, 2015, 38(4): 753-763. doi:10.1007/s10545-015-9838-4. [15] Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development[J]. Cell, 2019, 176(6): 1248-1264. doi:10.1016/j.cell.2019.01.021. [16] Adunka O, Gstoettner W, Knecht R, et al. Expression of hypoxia inducible factor 1 alpha and Von Hippel Lindau protein in human middle ear cholesteatoma[J]. Laryngoscope, 2003, 113(7): 1210-1215. doi:10.1097/00005537-200307000-00018. [17] Kuo CL, Shiao AS, Yung M, et al. Updates and knowledge gaps in cholesteatoma research[J]. Biomed Res Int, 2015, 2015: 854024. doi:10.1155/2015/854024. [18] 张鄂, 龚树生. 缺氧诱导因子-1α及诱导型一氧化氮合酶在中耳胆脂瘤上皮中的表达及意义[J]. 临床耳鼻咽喉头颈外科杂志, 2007, 21(10): 463-465. doi:10.3969/j.issn.1001-1781.2007.10.011. ZHANG Er, GONG Shusheng. Expression and Significance of HIF-1α and iNOS in human middle ear cholesteatoma epithelium[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2007, 21(10): 463-465. doi:10.3969/j.issn.1001-1781.2007.10.011. [19] Goda N, Dozier SJ, Johnson RS. HIF-1 in cell cycle regulation, apoptosis, and tumor progression[J]. Antioxid Redox Signal, 2003, 5(4): 467-473. doi:10.1089/152308603768295212. [20] Lacroix M, Riscal R, Arena G, et al. Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer[J]. Mol Metab, 2020, 33: 2-22. doi:10.1016/j.molmet.2019.10.002. [21] 岑瑞祥, 赵凯, 万浪, 等. 缺氧诱导因子-1α和BCL-2/腺病毒E1B19 kDa相关蛋白3在中耳胆脂瘤表达及意义[J]. 中国耳鼻咽喉头颈外科, 2019, 26(11): 621-623. doi:10.16066/j.1672-7002.2019.11.012. [22] Haruyama T, Furukawa M, Kusunoki T, et al. Expression of IL-17 and its role in bone destruction in human middle ear cholesteatoma[J]. ORL J Otorhinolaryngol Relat Spec, 2010, 72(6): 325-331. doi:10.1159/000319897. [23] 马志超, 熊观霞. 白细胞介素-17和干扰素-γ与慢性中耳炎骨质破坏的关系[J]. 中山大学学报(医学科学版), 2010, 31(4): 561-566. doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2010.0115. MA Zhichao, XIONG Guanxia. Relationship between IL-17 and IFN-γ with bone resorption in chronic otitis media[J]. Journal of Sun Yat-Sen University(Medical Sciences), 2010, 31(4): 561-566. doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2010.0115. [24] Ottaviani F, Neglia CB, Berti E. Cytokines and adhesion molecules in middle ear cholesteatoma. A role in epithelial growth? [J]. Acta Otolaryngol, 1999, 119(4): 462-467. doi:10.1080/00016489950181008. [25] Krzywinska E, Stockmann C. Hypoxia, metabolism and immune cell function[J]. Biomedicines, 2018, 6(2): 56. doi:10.3390/biomedicines6020056. [26] Gnanaprakasam JNR, Sherman JW, Wang RN. MYC and HIF in shaping immune response and immune metabolism[J]. Cytokine Growth Factor Rev, 2017, 35: 63-70. doi:10.1016/j.cytogfr.2017.03.004. [27] Sudhoff H, Dazert S, Gonzales AM, et al. Angiogenesis and angiogenic growth factors in middle ear cholesteatoma[J]. Am J Otol, 2000, 21(6): 793-798. [28] 陈雄, 孔维佳. 血管内皮生长因子在中耳胆脂瘤中的表达及其临床意义[J]. 中华耳科学杂志, 2004, 2(2): 129-132. doi:10.3969/j.issn.1672-2922.2004.02.014. CHEN Xiong, KONG Weijia. Expression of vascular endothelial growth factor and its clinical significance in middle ear cholesteatoma[J]. Chinese Journal of Otology, 2004, 2(2): 129-132. doi:10.3969/j.issn.1672-2922.2004.02.014. [29] 洪艺云, 叶胜难. MMP9及VEGF诱导血管生成在中耳胆脂瘤增殖与侵袭中的作用[J]. 中华耳科学杂志, 2012, 10(4): 504-509. [30] Bergers G, Brekken R, McMahon G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis[J]. Nat Cell Biol, 2000, 2(10): 737-744. doi:10.1038/35036374. [31] 马佐鹏, 李全成. HIF-1α及PI3K/Akt信号通路在中耳胆脂瘤中的表达及意义[J]. 河北医药, 2020, 42(15): 2259-2263. doi:10.3969/j.issn.1002-7386.2020.15.004. [32] Kouvaras E, Christoni Z, Siasios I, et al. Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors[J]. Biotech Histochem, 2019, 94(4): 283-289. doi:10.1080/10520295.2018.1556806. |
| [1] | 张国民,王茂华,高松,吴文斌,虞幼军. 持续灌流模式耳内镜下粘连性中耳炎手术疗效分析[J]. 山东大学耳鼻喉眼学报, 2026, 40(3): 16-19. |
| [2] | 朱明琼,李征,刘茹,田涛,彭婧利,吕倩怡,谭华霞. 基于OCT/OCTA的AI筛查系统在抗VEGF治疗糖尿病性黄斑水肿患者效果评价中的应用[J]. 山东大学耳鼻喉眼学报, 2026, 40(1): 68-73. |
| [3] | 宋瑾,尹慧,高娴,李永团. 坏死梭杆菌致成人中耳炎并发脑膜炎1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 96-100. |
| [4] | 周莹,王刚,王磊,张晓丽,韩浩伦,李保卫,孙喆喆,吴玮. 咽喉反流相关中耳炎1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2024, 38(6): 131-135. |
| [5] | 林云仙,马玲国. 咽鼓管圆枕淀粉样变性伴中耳积液1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2024, 38(4): 86-90. |
| [6] | 高欣妤,周函,刘丁丁,陆玲,陈杰,钱晓云. 中耳胆脂瘤伴高位颈静脉球1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2024, 38(3): 82-87. |
| [7] | 樊永将,黄卫,何成山,沈海涛,徐正,郝亚楠. SARS-CoV-2感染后成人急性分泌性中耳炎细胞因子水平分析[J]. 山东大学耳鼻喉眼学报, 2024, 38(2): 1-6. |
| [8] | 王丽雪,曾毅,王丽欣,彭先兵. 浸润毕罗芬明胶海绵在功能性鼻内镜鼻窦手术后应用效果的临床观察[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 16-25. |
| [9] | 徐恩沛,孙先勇. 渗出性年龄相关性黄斑变性并发视网膜色素上皮脱离的诊治进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 125-142. |
| [10] | 钟佳珂,王柏杨,伊海金. 以耳部症状首发、合并鼻咽占位的肉芽肿性多血管炎1例并文献复习[J]. 山东大学耳鼻喉眼学报, 2023, 37(1): 6-14. |
| [11] | 翟贯虹,于司函,张志强,于常旭,崔哲洙. 中耳胆脂瘤合并面瘫的手术后疗效分析[J]. 山东大学耳鼻喉眼学报, 2023, 37(1): 20-25. |
| [12] | 孙艳,姚浩,顾黎安. 布地奈德联合盐酸氨溴索鼓室内注射治疗成人分泌性中耳炎的疗效研究[J]. 山东大学耳鼻喉眼学报, 2022, 36(6): 77-82. |
| [13] | 王露萍,寇芳柠,王皓,张灿伟,王艳玲,尤冉,吴伟珍. 视网膜下高反射物质在抗VEGF治疗nAMD患者中对视力预后的影响[J]. 山东大学耳鼻喉眼学报, 2022, 36(6): 101-105. |
| [14] | 温立婷,李旭,高伟,胡田勇,曾宪海,查定军. 17例中耳术后迟发性面瘫的临床特征分析[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 1-5. |
| [15] | 李曼冯雪,王艳玲. 眼缺血综合征与缺血性脑卒中相关性研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 88-92. |
|
||