HDAC1、MAPK水平与慢性鼻-鼻窦炎伴鼻息肉患者糖皮质激素抵抗的关系

Relationship between HDAC1,MAPK levels and glucocorticoid resistance in patients with chronic rhinosinusitis and nasal polyps

目的:探讨组蛋白去乙酰化酶1(HDAC1)、丝裂原活化蛋白激酶(MAPK)水平与慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者糖皮质激素(GC)抵抗的关系。方法:选取2018年10月—2020年10月收治的CRSwNP患者60例,根据患者是否存在GC抵抗分为GC抵抗组(n=22)和GC敏感组(n=38)。测定两组GC治疗前、后HDAC1 mRNA及细胞外信号调节蛋白激酶(ERK)、c-Jun N末端蛋白激酶(JNK)、p38MAPK mRNA水平。利用受试者工作特征(ROC)曲线分析HDAC1、p38MAPK、ERK、JNK对CRSwNP患者GC抵抗发生的预测价值。将有差异的单因素纳入Logistic模型,行量化赋值,明确CRSwNP患者GC抵抗发生的危险因素。结果:治疗后,GC抵抗组HDAC1 mRNA表达量显著低于GC敏感组,p38MAPK mRNA、ERK mRNA、JNK mRNA表达量显著高于GC敏感组(t=18.425、19.213、18.721、19.694,均P<0.05)。经ROC曲线分析,HDAC1 mRNA、p38MAPK mRNA、ERK mRNA、JNK mRNA预测CRSwNP患者GC抵抗发生的曲线下面积分别为0.715(95%CI:0.570-0.860)、0.917(95%CI:0.849-0.985)、0.863(95%CI:0.754-0.971)、0.885(95%CI:0.795-0.973),均P<0.05。经多因素Logistic回归分析证实,HDAC1 mRNA<0.660(OR=1.386,95%CI:1.216-1.580)、p38MAPK mRNA≥0.428(OR=1.647,95%CI:1.342-2.021)、ERK mRNA≥0.571(OR=1.627,95%CI:1.234-2.145)、JNK mRNA≥0.510(OR=1.897,95%CI:1.342-2.682)是CRSwNP患者GC抵抗发生的危险因素。结论:HDAC1、MAPK水平与CRSwNP患者GC抵抗密切相关。

Objective:To investigate the relationship between histone deacetylase 1(HDAC1)and mitogen activated protein kinase(MAPK)levels and glucocorticoid(GC)resistance in patients with chronic rhinosinusitis with nasal polyps(CRSwNP).Methods:A total of 60 patients with CRSwNP in our hospital from October 2018 to October 2020 were selected and divided into GC resistance group(n=22)and GC sensitive group(n=38)according to whether the patients had GC resistance.HDAC1 mRNA,extracellular signal-regulated protein kinase(ERK)mRNA,C-Jun N-terminal protein kinase(JNK)mRNA and p38MAPK mRNA levels in both groups were determined before and after GC treatment.ROC curve was used to analyze the predictive value of HDAC1 mRNA,p38MAPK mRNA,ERK mRNA and JNK mRNA on GC resistance in patients with CRSwNP.The single factor with difference was included in the Logistic model and quantitative assignment was performed to clarify the risk factors for GC resistance in patients with CRSwNP.Results:The expression of HDAC1 mRNA in GC resistant group was significantly lower than that in GC sensitive group,and the expression of p38MAPK mRNA,ERK mRNA and JNK mRNA were significantly higher than that in GC sensitive group(t=18.425,19.213,18.721,19.694,all P<0.05).By ROC curve analysis,the areas under the curve of HDAC1 mRNA,p38MAPK mRNA,ERK mRNA and JNK mRNA predicting the occurrence of GC resistance in patients with CRSwNP were 0.715(95%CI:0.570-0.860),0.917(95%CI:0.849-0.985),0.863(95%CI:0.754-0.971)and 0.885(95%CI:0.795-0.973),respectively(P<0.05).Multivariate Logistic regression analysis showed that HDAC1 mRNA<0.660(OR=1.386,95%CI:1.216-1.580),p38MAPK mRNA≥0.428(OR=1.647,95%CI:1.342-2.021),ERK mRNA≥0.571(OR=1.627,95%CI:1.234-2.145),JNK mRNA≥0.510(OR=1.897,95%CI:1.342-2.682)were the risk factors for GC resistance in patients with CRSwNP.Conclusion:HDAC1 and MAPK levels are closely related to GC resistance in patients with CRSwNP.