慢性鼻窦炎伴鼻息肉鼻黏膜中纤维蛋白交联和降解相关调控基因表达异常  

Dysregulation of genes related to fibrin formation and degradation in nasal mucosa of patients with chronic rhinosinusitis with nasal polyps

作　　者：王明[1,2] 洪宇 卜祥婷 王成硕 张罗[1,2] Wang Ming;Hong Yu;Bu Xiangting;Wang Chengshuo;Zhang Luo(Department of Otorhinolaryngology Head and Neck Surgery and Department of Allergy,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China;Beijing Institute of Otolaryngology,Beijing Institute of Integrated Traditional Chinese and Western Medicine in Otolaryngology,Beijing Laboratory of Allergic Diseases(Beijing Municipal Education Commission),Beijing Key Laboratory of Nasal Diseases,Key Laboratory of Otolaryngology Head and Neck Surgery(Capital Medical University),Ministry of Education,,Beijing 100005,China)

机构地区：[1]首都医科大学附属北京同仁医院耳鼻咽喉头颈外科、过敏科,北京100730 [2]北京市耳鼻咽喉科研究所,北京市中西医结合耳鼻咽喉科研究所,过敏性疾病北京实验室(北京市教育委员会)、鼻病研究北京市重点实验室、耳鼻咽喉头颈科学教育部重点实验室(首都医科大学),北京100005

出　　处：《首都医科大学学报》2024年第2期246-251,共6页Journal of Capital Medical University

基　　金：国家重点研发计划项目(2022YFC2504100);国家自然科学基金项目(82171109,82025010);北京市属医学科研院所公益发展改革试点项目(JYY2023-1)。

摘　　要：目的研究慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)患者以及合并哮喘(asthma,AS)患者(CRSwNP+AS)鼻黏膜中纤维蛋白沉积及其相关调控基因的表达情况。方法利用免疫荧光染色评估鼻黏膜中纤维蛋白的沉积情况;利用实时荧光定量聚合酶链式反应检测纤维蛋白交联和降解相关调控基因的表达,以及糖皮质激素治疗后的基因表达变化。结果与对照组相比,CRSwNP鼻黏膜中有显著的纤维蛋白沉积,且呈交联状态,CRSwNP+AS组有更明显的纤维蛋白沉积。基因表达检测显示,促进纤维蛋白交联的基因-凝血因子ⅩⅢA1(factorⅩⅢA chain 1,F13A 1)和抑制纤维蛋白降解的基因-纤溶酶原激活物抑制物1(plasminogen activator inhibitor 1,PAI-1)在CRSwNP和CRSwNP+AS组的表达均升高,并且F13A1在CRSwNP+AS组的表达较CRSwNP显著更高;促进纤维蛋白降解的基因-组织型纤溶酶原激活因子(plasminogen activator tissue type,PLAT)在CRSwNP+AS组的表达显著低于CRSwNP和对照组;尿激酶型纤溶酶原激活因子(plasminogen activator urokinase,PLAU)的表达在两种类型的CRSwNP中均上调。CRSwNP+AS患者经糖皮质激素治疗,可显著下调F13A1、上调PLAT的表达。结论CRSwNP患者鼻黏膜中存在大量纤维蛋白沉积,可能与纤维蛋白交联和降解相关基因的表达失调有关,合并AS患者鼻黏膜中F13A1和PLAT的表达失调更为明显。Objective To explore the deposition of fibrin and the expression of genes related to fibrin formation and degradation in nasal mucosa of patients with chronic rhinosinusitis with nasal polyps(CRSwNP)and patients with CRSwNP comorbid asthma(CRSwNP+AS).Methods Immunofluorescence staining was used to evaluate the deposition of fibrin in the nasal mucosa.Real-time fluorescence quantitative polymerse chain reaction(RT-qPCR)was used to detect the expression of genes related to fibrin formation and degradation[factorⅩⅢA chain 1(F13A 1),plasminogen(PLG),plasminogen activator tissue type(PLAT),plasminogen activator urokinase(PLAU)and plasminogen activator inhibitor 1(PAI-1)]in nasal mucosa of CRSwNP,CRSwNP+AS and control subjects.The patients received glucocorticoid treatment.Results Compared with the control group,immunofluorescence staining showed obvious deposition of crosslinked fibrin in the nasal mucosa of patients with CRSwNP,and CRSwNP+AS group had more significant fibrin deposition.Gene expression analysis showed that the expression of F 13 A 1,a gene that promotes fibrin formation,and PAI-1,a gene that inhibits fibrin degradation,were both significantly increased in the CRSwNP and CRSwNP+AS groups.In addition,the expression of F 13 A 1 was significantly higher in CRSwNP+AS group than that in CRSwNP group.The expression of PLAT,which promotes fibrin degradation,was significantly lower in the CRSwNP+AS group than that in the CRSwNP and control groups.PLAU is upregulated in both types of CRSwNP.Glucocorticoid treatment significantly downregulates F 13 A 1 and upregulates the expression of PLAT in patients with CRSwNP+AS.Conclusion Patients with CRSwNP have excessive fibrin deposition in the nasal mucosa,which may be caused by the dysregulation of genes related to fibrin formation and degradation.Dysregulated F 13 A 1 and PLAT were more significant in CRSwNP+AS.

关 键 词：慢性鼻窦炎伴鼻息肉 哮喘 纤维蛋白 凝血因子ⅩⅢA 纤溶酶原激活因子 

分 类 号：R765[医药卫生—耳鼻咽喉科]