新疆医科大学学报

目的 探究慢性鼻-鼻窦炎伴鼻息肉患者鼻黏膜组织诱导缺氧因子-1α(HIF-1α)、黏蛋白5AC(MUC5AC)表达与糖皮质激素抵抗的关系。方法 选取开滦总医院耳鼻喉科2017年8月至2022年6月接诊的160例慢性鼻-鼻窦炎伴鼻息肉患者为研究对象。给予患者口服泼尼松龙(0.5 mg·kg^-1·d^-1,连续服用14 d)。治疗前后采用鼻息肉内镜评分系统进行评分，根据评分下降情况分为正常组(n=131)和抵抗组(n=29)。采用免疫组化和实时荧光定量PCR(RT-PCR)观察HIF-1α与MUC5AC在细胞内的表达位置和两者mRNA的表达水平。采用Pearson相关性分析HIF-1α与MUC5AC mRNA表达的相关性。将HIF-1α与MUC5AC mRNA的表达进行单因素和多因素Logistic回归分析和受试者工作特征曲线(ROC)分析。结果 抵抗组患者鼻黏膜组织中HIF-1α和MUC5AC mRNA的表达高于正常组(P<0.05)。病理分析显示，HIF-1α主要在细胞核中表达，在细胞质中部分表达；MUC5AC主要在细胞质内表达。Pearson相关性分析显示，患者鼻黏膜组织中HIF-1α与MUC5AC mRNA表达之间呈正相关(r=0.596,P<0.05)。多因素Logistic回归分析显示，HIF-1α高表达、MUC5AC高表达是糖皮质激素抵抗发生的独立危险因素(OR=3.268、3.057,P<0.05)。ROC曲线分析显示，以HIF-1αmRNA表达水平≥0.549和MUC5AC mRNA表达水平≥0.543作为预测糖皮质激素抵抗的分界点曲线下面积分别为0.804、0.706,灵敏度为68.70%、86.21%,特异度为76.34%、75.86%。结论 慢性鼻-鼻窦炎伴鼻息肉患者鼻黏膜组织中HIF-1α、MUC5AC表达水平与糖皮质激素抵抗关系密切，可以作为预测糖皮质激素治疗慢性鼻-鼻窦炎伴鼻息肉患者临床疗效的可靠参考指标。

Objective To explore the relationship between the expression of HIF-1αand MUC5AC in nasal mucosa and glucocorticoid resistance in patients with chronic rhinosinusitis and nasal polyps. Met-hods 160 patients with chronic rhinosinusitis with nasal polyps who were admitted to the hospital from August 2017 to June 2022 were selected as the study subjects. The patients were given prednisolone orally(0.5 mg·kg^-1·d^-1 for 14 consecutive days). Before and after thetreatment, the endoscopic polyp scoring standard was used to score according to the nasal polyp endoscopic scoring system, and the patients were divided into the normal group(n=131) and the resistance group(n=29) according to the decline of the score. Immunohistochemistry and RT-PCR were used to observe the expression position of HIF-1α and MUC5AC in cells and the mRNA expression level of both. Pearson correlation was used to analyze the correlation of HIF-1α and MUC5AC mRNA expression. The expression of HIF-1α and MUC5AC mRNA was subjected to univariate and multivariate Logistic regression analysis and ROC analysis. Results The expression of HIF-1α and MUC5AC mRNA in nasal mucosa of thepatients with resistance group were higher than that of normal group(P<0.05). Pathological analysis showed that HIF-1α was mainly expressed in the nucleus and partially in the cytoplasm. MUC5AC was mainly expressed in the cytoplasm. By Pearson correlation analysis, there was a positive correlation between the expression of HIF-1α and MUC5AC mRNA in nasal mucosa(r=0.596, P<0.05). Multivariate Logistic regression analysis showed that high expression of HIF-1α and MUC5AC was independent risk factor for glucocorticoid resistance(OR=3.268, 3.057, P<0.05). ROC curve analysis showed that when HIF-1α mRNA expression level ≥0.549 and MUC5AC mRNA expression level ≥ 0.543 were used as the dividing points for predicting glucocorticoid resistance, the areas under the curve were 0.804 and 0.706, respectively, with sensitivity of 68.70%, 86.21%, specificity of 76.34%, 75.86%. Conclusion The expression level of HIF-1α and MUC5AC in nasal mucosa of thepatients with chronic nasosinusitis and nasal polyps is closely related to glucocorticoid resistance, and it can be used as a reliable reference index to predict the clinical efficacy of glucocorticoid treatment in patients with chronic nasosinusitis and nasal polyps.