HO-1在慢性鼻-鼻窦伴鼻息肉患者鼻息肉组织中的表达及调节机制研究

目的探讨血红素氧合酶1(HO-1)在慢性鼻-鼻窦伴鼻息肉患者鼻息肉组织中的表达及调节机制.方法 50例慢性鼻-鼻窦伴鼻息肉患者为鼻息肉组织组,30例单纯鼻中隔偏曲患者的钩突黏膜组织为对照组.采用实时荧光定量RT-PCR、免疫组化、Western blot检测鼻息肉和钩突黏膜组织中HO-1表达情况.另取钩突黏膜组织体外培养,检测不同细胞因子(IL-17A,TGF-β1)和地塞米松(DEX)刺激鼻黏膜组织中HO-1 mRNA的调节作用.结果HO-1 mRNA在鼻息肉组织中表达水平明显高于钩突黏膜组织,差异具有统计学意义(P0.05).鼻息肉组织中HO-1阳性细胞多分布于黏膜下腺体、上皮细胞、炎性细胞;HO-1阳性细胞数明显多于对照组,差异具有统计学意义(P0.05).鼻息肉组织中HO-1蛋白表达水平明显高于对照组,差异具有统计学意义(P0.05).IL-17A可明显提升HO-1 mRNA表达水平;TGF-β1,DEX可明显降低HO-1 mRNA表达水平;且IL-17A,TGF-β1,DEX刺激具有浓度依赖性.DEX与IL-17A联合刺激组和DEX与TGF-β1联合刺激组的HO-1 mRNA表达量均明显低于IL-17A单独刺激组,差异具有统计学意义(P0.05).结论 HO-1作为拮抗氧化剂在鼻息肉组织氧化应激过程中被反馈性诱导上调,而糖皮质激素可抑制其表达上调.

Expression and Regulation Mechanism of HO-1 in Nasal Polyp Tissues of Patients with Chronic Rhinosinusitis with Polyps

ObjectiveTo investigate the expression and regulation of heme synthase 1 (HO-1) in nasal polyp tissues of patients with chronic rhinosinusitis with polyps (CRSwNP).MethodNasal polyp tissues of 50 cases of chronic rhinosinusitis with polyps were taken for the investigation and the uncinate process mucosa tissues of 30 cases with simple nasal septum deviation were collected as the control group at the same time.Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry and Western blot were used to detect the expression of HO-1 in the nasal polyp and the uncinate process mucosa tissues.Moreover,the uncinate process mucosa tissues were taken and cultured in vitro for the detection of different cytokines (IL-17A and TGF-β1) and HO-1 mRNA in the nasal mucosa stimulated by dexamethasone (DEX).ResultsThe expression level of mRNA HO-1 in nasal polyps was significantly higher than that in the mucosal tissues (P<0.05).HO-1 positive cells in nasal polyps were mostly distributed in the submucosal glands,epithelial cells and inflammatory cells;HO-1 positive cells were significantly more than those in the control group (P<0.05).The expression level of HO-1 protein in nasal polyps was significantly higher than that in control group (P<0.05).IL-17A could significantly enhance the level of mRNA HO-1 expression,TGF-beta 1 and DEX could significantly reduce the level of mRNA HO-1 expression,and the stimulation of IL-17A,TGF-beta 1 and DEX was concentration-dependent.The expression levels of HO-1 mRNA in the combined DEX and IL-17A-stimulated group and the combined DEX and TGF-β1-stimulated group were significantly lower those in the IL-17A-stimulated group (P<0.05).ConclusionHO-1 as an antagonistic antioxidant,can be up-regulated in a feedback way in the process of oxidative stress of the nasal polyp tissues,and glucocorticoids can inhibit its up-regulated expression.