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

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ⅩⅢ A1（factor ⅩⅢ A chain 1, F13A1）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。

Abstract

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 ［factor ⅩⅢ A chain 1 (F13A1)， 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 F13A1, 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 F13A1 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 F13A1 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 F13A1 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ⅩⅢ A / 纤溶酶原激活因子

Key words

chronic rhinosinusitis with nasal polyps / asthma; fibrin / factor ⅩⅢ A / plasminogen activator