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  • 學位論文

腎臟MDM2及p14ARF染色與慢性腎臟病的關係

The association between cellular expression of MDM2 and p14ARF with Chronic Kidney Disease

指導教授 : 張浤榮

摘要


前言: 根據衛生署民國九十八年的臺灣民眾十大死亡原因報告, 慢性腎臟病已居國人十大死因的第十位, 慢性腎臟病除可能因腎功能持續惡化而導致末期腎臟病外, 更會增加病患本身死亡的危險性(Wen, Cheng et al. 2008; Bowling, Feller et al. 2011)。而其致病機轉眾多, 細胞凋亡(Apoptosis process)是慢性腎臟病的眾多機轉之一, 而細胞凋亡指標( Apoptotic makers)與急性腎臟病之間的關係已有相關探討(Kaushal, Basnakian et al. 2004; Bengatta, Arnould et al. 2009; Havasi and Borkan 2011)。 本文欲探討這些與急性腎臟病有關的細胞凋亡路徑( Apoptosis pathway)上的Markers在慢性腎臟病組織切片上的表現, 是否也與臨床慢性腎臟病嚴重程度呈現相關。 材料及方法: 我們收集三年內共七十位診斷為慢性腎臟病的病患因各種原因接受腎臟切除手術。 回顧式地研究其腎臟MDM2及p14ARF之免疫組織化學染色與臨床慢性腎臟病嚴重程度間的關係。 結果: 臨床慢性腎臟病較為嚴重( eGFR < 45 ml/min/1.73 m2)的病患其比較臨床慢性腎臟病較為輕微( eGFR >= 45 ml/min/1.73 m2)的病患, 在血清肌酸酐及貧血均有顯著的差異性。 臨床慢性腎臟病較為嚴重的病患其腎臟組織切片比較臨床慢性腎臟病較為輕微的病患, 在腎絲球組織硬化指數、腎間質組織硬化指數有顯著的差異性。 在腎臟組織的正常腎小管之細胞質( NTc)及萎縮腎小管之細胞質( ATc), p14ARF的染色程度強的均落在慢性腎臟病較為嚴重這一組( p值分別為0.009及0.011, 均達統計顯著差異)( 如Table 7-1b及Figure 4)。 進一步分析發現病患年齡大於等於六十五歲、 BMI組成( 體重過輕與體重過重)、臨床診斷為Urothelial cell carcinoma ( UCC) 、血清肌酸酐 ( mg/dl)偏高、正常腎小管之細胞質( NTc)的p14ARF染色強度強等之變項均對於慢性腎臟病較為嚴重是較為危險( 其Odds ratio及 95% Confidence Interval分別為2.81及1.06-7.44; 66.00及6.08- 716.18; 10.50 及2.34-47.04; 3.75及1.08-13.07; 558.00及48.24-6453.81; 5.76及1.62-20.45)。 結論: 這個研究指出正常腎臟腎小管細胞質的p14ARF免疫組織化學染色表現強度與臨床慢性腎臟病嚴重程度呈現正相關。

並列摘要


Objectives According to Department of Health report of the rank of public mortality etiolgy, chronic kidney disease had been the tenth rank. Chronic kidney disease not only causes patient mortality by itself, Chronic kidney disease related morbidities also induce patient mortality(Wen, Cheng et al. 2008; Bowling, Feller et al. 2011). One of the pathogenesis of Chronic kidney disease was apoptosis, the correlation between apoptotic makers with acute kidney injury had been reported before(Kaushal, Basnakian et al. 2004; Bengatta, Arnould et al. 2009; Havasi and Borkan 2011), therefore, we studied if these apoptotic pathway makers also had the correlation to the severity of Chronic kidney disease on our kidney tissue samples. Methods We totally collect seventy Chronic kidney disease patients who received Nephroectomy due to all kinds of etiologies within three years. We retrospectively studies the correlation between Immunohistochemical stains of these kidney tissues by MDM2 and p14ARF with the clinical severity of Chronic kidney disease. Results We showed the glomerular and interstitial fibrosis scores had the significant difference between the advanced chronic kidney disease( eGFR < 45 ml/min/1.73 m2) and non- advanced chronic kidney disease( eGFR >= 45 ml/min/1.73 m2). In the area of normal tubular cytoplasm and atrophy tubular cytoplasm, p14ARF had stronger staining in the group of advanced chronic kidney disease( p vaule were 0.009 and 0.011 respectively,statistical significant difference). After further analysis, we found the patients who were over sixty five years- old, abnormal BMI( too light or over weight), had the diagnosis of Urothelial cell carcinoma (UCC), high serum Creatinine level and stronger staining p14ARF of normal tubular cytoplasm all had higher risk for advanced chronic kidney disease(Odds ratio and 95% Confidence Interval were 2.81 and 1.06-7.44; 66.00 and 6.08-716.18; 10.50 and 2.34-47.04; 3.75 and 1.08-13.07;558.00 and 48.24-6453.81;5.76 and 1.62-20.45). Conclusion We showed the Immunohistochemical stain of p14ARF over normal tubular cytoplasm area had positive correlation with the clinical severity of Chronic kidney disease.

參考文獻


"HUGO Gene Nomenclature Committee ".
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Bengatta, S., C. Arnould, et al. (2009). "MMP9 and SCF protect from apoptosis in acute kidney injury." J Am Soc Nephrol 20(4): 787-797.

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