pendrin在慢性鼻-鼻窦炎黏膜中的表达及其与黏蛋白5AC表达的相关性

Expression and relationship of pendrin and MUCSAC in patients with chronic rhinosinusitis

目的探讨pendrin在慢性鼻-鼻窦炎（CRS）中的表达及与黏蛋白5AC（MUC5AC）的相关性。方法取伴或无息肉的CRS患者上颌窦窦口黏膜各30例分别作为伴息肉CRS组和无息肉CRS组、另取10例单纯性上颌窦囊肿患者的上颌窦口前壁近钩突部位的黏膜作为对照组，采用HE染色观察各组鼻窦黏膜的组织形态学改变，糖原过碘酸雪夫染色（PAS染色）检测各组鼻窦黏膜中总黏蛋白的表达情况，免疫组织化学方法、实时荧光定量PCR法和免疫印迹法检测各组鼻窦黏膜中pendrin和MUC5AC的表达情况。结果在伴息肉CRS组和无息肉CRS组鼻窦黏膜中均可观察到黏膜增厚，杯状细胞增生，上皮纤毛部分缺失，腺体增生，炎性细胞浸润；pendrin蛋白主要表达于鼻窦黏膜上皮细胞的顶膜，其次为黏膜下腺体细胞；MUC5AC主要表达于鼻窦黏膜上皮的杯状细胞和假复层纤毛柱状细胞，少量表达于黏膜下腺体细胞。伴息肉CRS组和无息肉CRS组鼻窦黏膜中总黏蛋白、pendrin蛋白、MUC5AC阳性表达率（86．7％和80．0％比20．0％、73．3％和70．0％比10．0％、83．3％和76．7％比20．0％）、pendrin的mRNA及蛋白的相对表达水平（1．685±0．111和1．537±0．262比1．012±0．167及2．066±0．188、1．996±0．153比1．000±0．169）、MUC5AC的mRNA相对表达水平（1．861±0．718、1．562±0．428比1．004±0．094）均显著高于对照组（均P〈0．05）。pendrinmRNA的表达水平与MUC5ACmRNA表达水平呈正相关（r=0．670，P=0．006和r=0．713，P=0．003）。结论在CRS黏膜中表达上调的pendrin与MUC5AC的表达增加有一定关联，前者可能是CRS中黏液高分泌的重要因子。

Objective To explore the expression of pendrin in sinonasal mucosal tissue of patients with chronic rhinosinusitis （CRS） and examine its relationship with mucinSAC （MUCSAC）. Methods Thirty mucosal tissue （located on anterior wall of maxillary sinus ostium and close to uncinate process） of patients with CRS with or without nasal polyps and 10 normal sinonasal mucosal tissue located at the same sites as CRS were collected. Histological changes of sinonasal mucosa were examined by hematoxylin and eosin （HE） staining. The expression of total mucins was evaluated by periodic acid Schiff staining （PAS）. And the expressions of pendrin and MUCSAC in sinonasal mucosa were determined by immunohistochemistry （IHC）, quantitative real-time polymerase chain reaction （qRT-PCR） and Western blot. Results The tissue samples demonstrated mucosal thickening, goblet cell hyperplasia and metaplasia, epithelial cilia partial deletion, glandular hyperplasia and a dense infiltration of inflammatory cells in CRS with or without nasal polyps. IHC revealed that positive pendrin was expressed dominantly at apical membrane of epithelial cells and sparsely in submucosal glandular cells, there was a positive expression rate of CRS with nasal polyps and CRS without nasal polyps; MUCSAC was expressed abundantly in goblet ceils and pseudostratified ciliated columnar epithelium cells and weakly in submucosal glandular cells in CRS. There were significant increases in positive expression rate of total mucins production, pendrin and MUCSAC in patients of CRS with nasal polyps or without nasal polyps than those in control （ 86.7% and 80. 0% vs20. 0%, 73.3% and 70. 0% vs 10.0%, 83.3% and 76. 7% vs 20.0%, all P〈0.05）; the relative expression levels of mRNA and protein expression of pendrin were significantly greater in patients of CRS with or without nasal polyps than those in controls （ 1. 685 ± 0. 111 and 1. 537 ± 0. 262 vs 1. 012 ± 0. 167, 2. 066 ± 0. 188 and 1. 996 ± 0. 153 vs 1. 000 ± 0. 169, all P 〈 0. 05 ）. The relative expression levels of mRNA expression of MUC5AC were significantly greater in patients of CRS with or without nasal polyps than in controls （ 1. 861 ± 0. 718 and 1. 562 ± 0. 428 vs 1. 004 ± 0. 094, P 〈 0. 05 ）. And the expression level of pendrin mRNA was positively correlated with that of MUC5AC mRNA in patients with CRS （ r = 0. 670, P = 0. 006 and r = 0. 713, P = 0. 003 ）. Conclusions An up-regulation of pendrin is correlated with an over- expression of MUC5AC in patients with CRS. And pendrin is an important cause of mucus hypersecretion in CRS.