缺氧誘導因子在鼻息肉中的表現與臨床相關性

The Expression of Hypoxia-inducible factor 1α in nasal polyps and its clinical correlation

許英哲(Ying-Che Hsu)

指導教授 ： 郭文烈

高雄醫學大學/醫學院/醫學研究所/碩士(2006年)

摘要

慢性鼻竇炎併鼻息肉主要是源自於上頜竇，篩竇及中鼻甲附近區域的發炎反應，但是其詳細的病因以及發生機轉仍不清楚，在鼻科學中屬於難治療的疾病。感染，發炎或壓力可能是鼻息肉的成因之ㄧ。鼻息肉常常造成病人生活上的不便，而鼻息肉的高復發率也造成許多醫療資源上的負擔。缺氧誘導因子(Hypoxia inducible factor, HIF-1) 為一存在於細胞之內的轉錄因子，由HIF-1α及 HIF-1βsubunits二聚體所構成。在一般正常氧氣的條件下HIF-1α會在5分鐘之內代謝掉，但是在缺氧的環境下其分解途徑會被阻斷，於是進入細胞核中使得下游基因開始表現。在惡性腫瘤中缺氧誘導因子的表現增加已被報告，但是在鼻息肉等良性腫瘤的表現仍不清楚。本實驗即試圖探討缺氧誘導因子在慢性鼻竇炎併鼻息肉病患中組織的表現情形與下鼻甲黏膜的表現之差異，並探討與疾病嚴重度的相關性。45位即將進行鼻竇內視鏡手術的病人為實驗組，在手術當中取其鼻息肉組織做HIF-1α, VEGF與CD34免疫組織染色分析，並以鼻竇電腦斷層結果，使用Lund-Mackay法判斷其臨床嚴重度; 另取39位接受鼻道成型手術，無鼻竇炎病史之病患的下鼻甲黏膜組織為對照組。結果顯示在實驗組的組織中缺氧誘導因子以及血管內皮生長因子的表現均較對照組高，且呈現有意義的差異(P<0.05)。但是微血管密度在鼻息肉組與對照組之間則無統計學上的差異。另外以real-time RT-PCR的方法來檢驗鼻息肉組織以及對照組之間HIF-1α mRNA的表現，發現鼻息肉的HIF-1α mRNA與對照組並沒有顯著的差異。HIF-1α蛋白質在鼻息肉的表現與病患臨床症狀的時間長短以及電腦斷層的嚴重程度並沒有相關性。
我們認為在鼻息肉組織中缺氧誘導因子蛋白質的表現增加也許在鼻息肉的生成機制中扮演一定的角色，但是其mRNA與蛋白質之間表現的關連與機制需要更進一步的研究。

關鍵字

缺氧誘導因子 ； 鼻息肉

並列摘要

Nasal polyps are originated from maxillary sinus, ethmoid sinus and the area near middle meatus, and its etiology and mechanism are still not well-known. The infection, inflammation and pressure, may be the pathogenesis.. Nasal polyps are recalcitrant disease in clinical rhinology. They make inconvenience and disturbance to patient’s daily life and the high recurrence rate also make a burden to medical insurance. Hypoxia-inducible factor-1 (HIF-1) is a DNA binding protein, which consist of a heterodimer HIF-1αand HIF-1βsubunits. HIF-1α protein is subject to rapid degradation at normoxia with short half-life (less than 5 minutes). In hypoxia condition, the degradation of HIF-1α is blocked leading to accumulation and induce downstream gene expression.
The study investigated the expression of HIF-1α protein in nasal polyps with chronic sinusitis compared to the inferior turbinate mucosa, and the correlation to the severity of the disease. Surgical specimen of polyps from forty-five patient underwent endoscopic sinus surgery had the HIF-1α, VEGF and CD34 immunohistochemical staining. The severity of the disease was judged by the Lund-Mackay system from CT scanning. The control group consisted of 39 patients underwent septomeatal plasty without history of chronic sinusitis. The result showed that the expression of HIF-1α and VEGF were significantly increased in nasal polyps than control group, but the microvessel density had no difference. We also perform the real time RT-PCR to examine the HIF-1α mRNA in the nasal polyps, and the result showed no difference between the nasal polyps and turbinate mucosa.
We suggest that hypoxia inducible factor-1α protein may play a role in the pathogenesis of nasal polyps. However, the discrepancy between the HIF-1α mRNA and protein need to be elucidated.

並列關鍵字

hypoxia inducible factor ； nasal polyp

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