摘要
目的探究咽喉反流通过NF-κB信号通路介导炎症反应对声带白斑患者声带黏膜的影响。方法选取2015年6月至2017年6月在深圳市人民医院耳鼻咽喉头颈外科行声带白斑切除手术的患者,根据反流性喉炎症状指数量表(RSI)及反流性喉炎体征指数量表(RFS)及24h双通道测酸结果将患者随机分为反流组(n=25)、反流+质子泵抑制剂(PPI)组(n=26),选取同期无咽喉反流患者为阴性对照(非反流组,n=30)。反流+PPI组口服艾司奥美拉唑镁肠溶片,反流组与非反流组口服安慰剂,记录患者术前及术后8周RSI、RFS测定结果,并取患者术后8周声带黏膜标本,做HE染色检测声带黏膜病理组织学变化;用ELISA法检测声带黏膜中TNF-α、IL-1β、IL-6、IL-10、IL-13含量;用Western blot法检测声带黏膜中Claudin-3、Occludin、ZO-1及p-p65、p-IKK、p-IκB、IκB-α蛋白含量;术后12个月随访患者声带白斑复发情况。结果反流+PPI组患者声带白斑复发率(26.9%)显著低于反流组(76.0%)(P<0.05);术后给予PPI治疗8周后,反流+PPI组RSI、RFS、组织病理学评分显著低于反流组(均P<0.05),声带黏膜组织上皮结构完整性、纤维异型增生、炎性细胞浸润较反流组明显改善;反流+PPI组患者声带黏膜促炎因子TNF-α、IL-1β、IL-6含量显著低于反流组(均P<0.05),IL-10、IL-13含量显著高于反流组(均P<0.05);且Claudin-3、Occludin、ZO-1、IκB-α蛋白表达显著升高(均P<0.01),p-p65、p-IKK、p-IκB蛋白表达显著低于反流组(均P<0.01)。结论伴有咽喉反流的声带白斑病患者,给予PPI抑酸治疗后,可明显减轻咽喉反流症状,降低声带白斑复发率,可能是通过下调NF-κB信号通路相关因子,减少促炎因子的分泌,并增强声带黏膜屏障功能。
Objective To investigate the effect of NF-κB signaling pathway-mediated laryngopharyngeal reflux(LPR)on vocal cord mucosa in patients with vocal leukoplakia.Methods Patients who underwent the resection of vocal leukoplakia in the Department of Otorhinolaryngology-Head and Neck Surgery of Shenzhen People’s Hospital between June 2015 and June 2017 were selected and divided into two groups according to the results of reflux symptom index(RSI),reflux finding score(RFS),and 24 hdual-channel intraesophageal pH-metry:reflux group(n=25)and reflux+PPI group(n=26).Meanwhile,patients without LPR served as negative control group(non-reflux group,n=30).Patients in the reflux+PPI group were treated with enteric-coated tablets of omeprazole magnesium,while those in the reflux group and the non-reflux group received oral placebo.The RSI and RFS were recorded before and 8 weeks after the operation.The vocal cord mucosa specimens were taken at postoperative 8 weeks for the detections of histopathological changes by HE staining,levels of TNF-α,IL-1β,IL-6,IL-10 and IL-13 by ELISA,as well as the levels of claudin-3,occludin,ZO-1 and p-p65,p-IKK,p-IκB and IκB-αby Western blotting.Thereafter,the recurrence rate of vocal leukoplakia was recorded during the postoperative 12-month follow-up.Results The recurrence rate of vocal leukoplakia in the reflux+PPI group was significantly lower than that in the reflux group(26.9%vs.76.0%,P<0.05).At postoperative 8 weeks,the RSI,RFS,and histopathology scores in the reflux+PPI group were significantly lower than those in the reflux group(P<0.05).The histopathological changes including epithelial structural integrity,fibrous dysplasia,and inflammatory cell infiltration were better in the reflux+PPI group than in the reflux group(P<0.05).The reflux+PPI group had lower levels of TNF-α,IL-1βand IL-6 as well as higher levels of IL-10 and IL-13 than the reflux group did(P<0.05).The reflux+PPI group had higher protein expression levels of claudin-3,occludin,ZO-1 and IκB-αas well as lower protei
作者
刘倩
吕颜露
Liu Qian;Lv Yanlu(Department of Otolaryngology-Head and Neck Surgery Shenzhen People's Hospital,Shenzhen 518010,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2019年第1期32-37,共6页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
深圳市科技计划项目(No.JCYJ20170307095642983)
关键词
咽喉反流
声带白斑
NF-ΚB信号通路
质子泵抑制剂
黏膜屏障
laryngopharyngeal reflux
vocal leukoplakia
NF-κB signaling pathway
proton pump inhibitor
mucosal barrier
