慢性腎臟疾病病人腎臟組織中缺氧誘導因子-1α的表現

Renal expression of hypoxia inducible factor-1α in patients with chronic kidney disease

洪東衛(Tung-Wei Hung)

指導教授 ： 張浤榮

中山醫學大學/醫學院/醫學研究所/碩士(2011年)

https://doi.org/10.6834/CSMU.2011.00139

摘要

缺氧誘導因子-1α ( Hypoxia Inducible Factor-1α, HIF-1α)在腎臟間質纖維化的病理過程扮演了重要的角色。然而人類腎臟組織裡HIF-1α的表現跟腎臟功能及腎臟纖維化程度的關係還沒有很清楚。
這是一個回溯性的研究，利用病理檢查，免疫組織化學特殊染色分析(Immunohistochemical analysis) 來評估70個因為腎細胞癌(Renal Cell Carcinoma)、 尿路上皮癌 (Urothelial Cell Carcinoma)和腎膿瘍(Renal Abscess)，而接受腎臟切除手術所取下的腎臟檢體中HIF-1α的表現。把這70個病人分為兩組：一組37人表現出低的HIF-1α，。另一組33人表現出高的HIF-1α。透過完整的病歷回顧及病理檢查，我們來比較這兩組的臨床基本資料，包括年紀、性別、身高體重指數、有否抽煙、有無糖尿病、有無高血壓、血清肌酐酸的值、估計腎絲球過濾速率、血紅素的值、疾病種類以及腎小球和腎間質纖維化的高低。
結果顯示腎臟組織HIF-1α的表現跟血清肌酐酸的值(p = 0.03)，估計腎絲球過濾速率(p = 0.02)，腎絲球硬化程度(p = 0.004)以及腎間質纖維化程度(p = 0.013)有統計上的差異。血清肌酐酸的值低，估計腎絲球過濾速率高，腎絲球硬化程度以及腎間質纖維化程度低的腎臟組織有高的HIF-1α表現。除此之外，邏輯式迴歸的多變項逐步分析顯示，腎間質纖維化程度是腎臟組織HIF-1α表現強度的預測因子，而且呈現負相關。
這個研究顯示腎臟組織HIF-1α的表現跟腎臟組織纖維化的程度有關，腎臟組織HIF-1α的表現在慢性腎臟病的病理過程中扮演了一個角色。確切的作用機轉，值得更進一步的研究。

關鍵字

缺氧誘導因子-1α ； 慢性腎臟疾病 ； 腎臟纖維化

並列摘要

It has been proven that hypoxia inducible factor-1α (HIF-1α) plays a role in the pathogenesis of renal interstitial fibrosis. However, the relationship of HIF-1α expression intensity in human renal tissue with degree of renal function or renal fibrosis has not been investigated.
We performed a retrospective study of 70 patients undergoing unilateral or bilateral nephrectomy because of renal cell carcinoma, urothelial cell carcinoma, or renal abscess. Immunohistochemical analysis of HIF-1α expression in human renal tissue was performed. The patients were divided into 2 groups: one (n = 37) with low intensity of HIF-1α expression and one (n = 33) with high intensity of HIF-1α expression.
The intensity of renal HIF-1α expression was significantly associated with serum creatinine level (p = 0.005), estimated glomerular filtration rate (p = 0.02), fibrosis score of the interstitum (p = 0.013) and glomerular sclerosis (p = 0.004). High intensity of HIF-1α expression tended to associated with lower serum creatinine, higher estimated glomerular filtration rate, low interstitial fibrosis score and low glomerular sclerosis. In addition, multivariate analysis by stepwise logistic regression was performed and it demonstrated that interstitial fibrosis was the only independent factor associated with the intensity of renal HIF-1α expression ( p= 0.005).
This study demonstrated a correlation between intensity of HIF-1α expression and degree of renal interstitial fibrosis. The association demonstrated elevated HIF-1α expression in less severe kidney disease. HIF-1α intensity of renal expression might play a role in the pathogenesis of chronic kidney disease.

並列關鍵字

hypoxia inducible factor-1α ； chronic kidney disease ； renal fibrosis

參考文獻

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