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[重启手术治疗2型炎症性慢性鼻-鼻窦炎伴鼻息肉患者鼻黏膜的形态学及分子生物学变化观察]

[Observation of morphological and molecular biological changes of nasal mucosa in patients with type 2 inflammation chronic rhinosinusitis with nasal polyps after Reboot surgery].

作者信息

Chen Xubo, Zhu Xinhua, Zhu Yu, Zhou Zheng, Fu Zhihui, Liu Hongbing

机构信息

Department of otorhinolaryngology,the Second Affiliated Hospital of Nanchang University,Nanchang,330006,China.

Jiangxi Otorhinolaryngology Clinical Medical Research Center.

出版信息

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2025 Sep;39(9):809-816. doi: 10.13201/j.issn.2096-7993.2025.09.003.

DOI:10.13201/j.issn.2096-7993.2025.09.003
PMID:40898892
Abstract

To explore the effect, postoperative mucosal pathological changes and molecular biological changes of reboot operation for type 2 inflammation chronic rhinosinusitis with nasal polyps(CRSwNP) patients, and to provide theoretical basis for the clinical application of this kind of operation. We collected 29 patients who were diagnosed with CRSwNP with type 2 inflammatino response and underwent Reboot surgery from June 2022 to August 2023, and 27 patients who were diagnosed with deviated septum and underwent simple submucosal resection of the septum as the control group. We conducted nasal symptom scoring, endoscopic sinusitis scoring, and CT scanning of the sinuses before and after surgery, as well as HE staining, immunohistochemical staining, and detection of inflammatory factors using Elisa kits at the time of surgery, 1, 3, and 6 months postoperatively. We also observed the ultrastructural changes using transmission electron microscopy and scanning electron microscopy, and performed proteomic analysis of the mucosa in the ethmoid sinus area of the sinusitis patients at the time of surgery and 6 months postoperatively. After 6 months of postoperative follow-up, CT scores of the nasal cavity and sinuses had gradually decreased compared with the preoperative period. The VAS score of main symptoms, SNOT-22 score and Lund-Kennedy endoscopic score were decreased after 12 months follow-up. The histological morphology of the mucosa in the area of the screen was significantly improved compared with the preoperative period, with a reduction in the number of eosinophils. The levels of inflammatory factors such as IL-4 and IL-5 et al. in the mucosa of the area of the screen were gradually reduced compared with the preoperative period. The histological morphology, ultrastructure, and cilia structure of the mucosa in the area of the screen were gradually improved compared with the preoperative period, though not recovered completely. The number of CD4⁺T and CD8⁺T cells not changed significantly before and after the surgery yet. By conducting proteomic analysis of the ethmoidal sinus mucosa before and after surgery, differential proteins were selected, and bioinformatics analysis was conducted on the differentially expressed proteins. By using cytoHubba to identify hub genes and intersecting them with the genes related to chronic sinusitis, we found that MMP9 expression increased in non-type 2 CRS and type 2 CRS in sequence, while ACTC1 expression decreased in non-tpye 2 CRS and type 2 CRS in sequence. Reboot surgery can improve the postoperative symptoms and signs of patients, improve the pathological morphology of the mucosa, and influence the expression of protein after surgery. However, the surgery may not have a significant impact on the distribution of T cell subpopulations and inflammation signal pathway in the nasal mucosa.

摘要

探讨重启手术对2型炎症性慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者的疗效、术后黏膜病理变化及分子生物学变化,为该类手术的临床应用提供理论依据。我们收集了2022年6月至2023年8月期间诊断为2型炎症反应的CRSwNP并接受重启手术的29例患者,以及诊断为鼻中隔偏曲并接受单纯鼻中隔黏膜下切除术的27例患者作为对照组。我们在手术前、后进行了鼻症状评分、鼻窦炎内镜评分及鼻窦CT扫描,在手术时、术后1个月、3个月和6个月进行了HE染色、免疫组化染色及使用酶联免疫吸附测定试剂盒检测炎症因子。我们还使用透射电子显微镜和扫描电子显微镜观察了超微结构变化,并对鼻窦炎患者筛窦区域黏膜在手术时及术后6个月进行了蛋白质组学分析。术后6个月随访时,鼻腔和鼻窦的CT评分较术前逐渐降低。随访12个月后,主要症状的视觉模拟评分(VAS)、鼻窦结局测试-22(SNOT-22)评分及Lund-Kennedy内镜评分均降低。筛区黏膜的组织形态较术前明显改善,嗜酸性粒细胞数量减少。筛区黏膜中白细胞介素-4(IL-4)、白细胞介素-5等炎症因子水平较术前逐渐降低。筛区黏膜的组织形态、超微结构及纤毛结构较术前逐渐改善,但未完全恢复。手术前后CD4⁺T细胞和CD8⁺T细胞数量无明显变化。通过对手术前后筛窦黏膜进行蛋白质组学分析,筛选出差异蛋白,并对差异表达蛋白进行生物信息学分析。通过使用cytoHubba识别枢纽基因并将其与慢性鼻窦炎相关基因进行交集分析,我们发现基质金属蛋白酶9(MMP9)表达在非2型CRS和2型CRS中依次升高,而心肌肌动蛋白1(ACTC1)表达在非2型CRS和2型CRS中依次降低。重启手术可改善患者术后症状和体征,改善黏膜病理形态,并影响术后蛋白质表达。然而,该手术可能对鼻黏膜中T细胞亚群分布及炎症信号通路无显著影响。

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