Luo Qing, Zhu Hengtao, Feng Kun, Huang Xiaoyan, Jing Xueling, Zhang Jian
Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, China. Emial: zhangjian115123 @126.com.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015 Feb;50(2):138-44.
To investigate the expression of hypoxia inducible factor-1α (HIF-1α) in chronic rhinosinusitis (CRS) and relationship with mucin MUC5AC, MUC5B secretion.
The expression of HIF-1α, MUC5AC and MUC5B were measured by immunohistochemistry (IHC), Western Blot and reverse transcription polymerase chain reaction (RT-PCR) in CRS with or without nasal polyps (CRSwNP: twenty-three or CRSsNP:twenty) and fifteen normal sinus mucosa without CRS. The relationship between HIF-1α and MUC5AC,MUC5B were analyzed by SPSS 16.0 software.
PAS and IHC showed that HIF-1α, MUC5AC, MUC5B, total mucins were expressed in nuclear of epithelium and gland cells, which were higher than normal control (t values in epithelium cells were 8.650, 9.305, 9.382, 8.524, 7.533, 5.417, 5.507, 5.556, all P < 0.05; t values in gland cells were 8.285, 7.098, 6.798, 7.308, 8.574, 7.933, 6.798, 7.308, all P < 0.05), but there was no significant difference between CRSwNP and CRSsNP (t values in epithelium cells were 0.734, 0.415, 0.572, 0.248, all P > 0.05; t values in gland cells were 0.331, 0.662, 0.249, 0.644, P > 0.05).Western Blot revealed that HIF-1α protein in CRSwNP and CRSsNP were higher than in normal contral (t values were 3.522, 3.314, respectively, P < 0.05). The relative expression levels of HIF-1α, MUC5AC,MUC5B mRNA in CRSwNP and CRSsNP were 1.35 ± 0.84, 1.36 ± 0.94, 0.81 ± 0.54,0.78 ± 0.46, 1.13 ± 1.00, 1.22 ± 1.02. But the relative expression levels of HIF-1α, MUC5AC,MUC5B mRNA in control subjects were 0.43 ± 0.34, 0.42 ± 0.36, 0.48 ± 0.42. There were significant differences between the groups of CRSwNP and control subiects (t values were 4.087, 4.089, 2.519, 2.550, 2.738, 2.955, respectively, all P < 0.05). There was a positive correlation among the expression of HIF-1α and MUC5AC, 5B mRNA in CRSwNP (r values were 0.474,0.464, respectively, all P < 0.05). There was a positive correlation among the expression of HIF-1α and MUC5AC, 5B mRNA in CRSsNP (r values were 0.477,0.514, respectively, all P < 0.05).
HIF-1α, MUC5AC and MUC5B expression were upregulated in CRS with or without nasal polyps, indicating CRS is a disease of mucus hypersecretion and there is a close association between HIF-1α with hypersecretion of MUC5AC and MUC5B in mucus.
探讨缺氧诱导因子-1α(HIF-1α)在慢性鼻-鼻窦炎(CRS)中的表达及其与黏蛋白MUC5AC、MUC5B分泌的关系。
采用免疫组织化学(IHC)、蛋白质免疫印迹法(Western Blot)及逆转录聚合酶链反应(RT-PCR)检测23例伴鼻息肉的慢性鼻-鼻窦炎(CRSwNP)、20例不伴鼻息肉的慢性鼻-鼻窦炎(CRSsNP)及15例正常鼻窦黏膜组织中HIF-1α、MUC5AC和MUC5B的表达。运用SPSS 16.0软件分析HIF-1α与MUC5AC、MUC5B的关系。
过碘酸雪夫染色(PAS)及免疫组织化学结果显示,HIF-1α、MUC5AC、MUC5B及总黏蛋白在上皮细胞核及腺泡细胞中均有表达,且均高于正常对照组(上皮细胞中t值分别为8.650、9.305、9.382、8.524、7.533、5.417、5.507、5.556,均P<0.05;腺泡细胞中t值分别为8.285、7.098、6.798、7.308、8.574、7.933、6.798、7.308,均P<0.05),但CRSwNP与CRSsNP组间差异无统计学意义(上皮细胞中t值分别为0.734、0.415、0.572、0.248,均P>0.05;腺泡细胞中t值分别为0.331、0.662、0.249、0.644,P>0.05)。蛋白质免疫印迹法显示,CRSwNP和CRSsNP组中HIF-1α蛋白表达高于正常对照组(t值分别为3.522、3.314,均P<0.05)。CRSwNP和CRSsNP组中HIF-1α、MUC5AC、MUC5B mRNA的相对表达量分别为1.35±0.84、1.36±0.94、0.81±0.54、0.78±0.46、1.13±1.00、1.22±l.02,而正常对照组中HIF-1α、MUC5AC、MUC5B mRNA的相对表达量分别为0.43±0.34、0.42±0.36、0.48±0.42,CRSwNP组与正常对照组间差异有统计学意义(t值分别为4.087、4.089、2.519、2.550、2.738、2.955,均P<0.05)。CRSwNP组中HIF-1α与MUC5AC、MUC5B mRNA表达呈正相关(r值分别为0.474、0.464,均P<0.05)。CRSsNP组中HIF-1α与MUC5AC、MUC5B mRNA表达呈正相关(r值分别为0.477、0.514,均P<0.05)。
伴或不伴鼻息肉的CRS中HIF-1α、MUC5AC及MUC5B表达均上调,提示CRS为黏液高分泌性疾病,且HIF-1α与黏液中MUC5AC、MUC5B高分泌密切相关。