糖尿性肾病变TNF-α与IL-基因多型性之探讨.docVIP

糖尿性腎病變TNF-α與IL-10基因多型性之探討 Gene Polymorphism of TNF-α and IL-10 in Diabetic Nephropathy Kung, Wan-Ju 指導教授：莊秀琪 Chaung, Hso-Chi 【摘要】 糖尿性腎病變是由糖尿病所引發之併發症，患者需仰賴血液透析以維持生理機能。然而在血液透析的過程中會促使促發炎細胞激素的產生，例如：TNF-α、IL-2、IL-6和IFN-γ等。TNF-α為一促發炎細胞激素，誘導細胞凋亡和調控其他發炎物質之分泌，例如：MCP-1。MCP-1會促使腎小管組織間隙發炎反應、腎小管萎縮以及腎臟纖維化。IL-10為細胞激素網中具有抗發炎作用之細胞激素，可抑制促發炎細胞激素基因表現與合成之功能。研究指出TNF-α與IL-10基因多型性與急性腎衰竭患者死亡率有關。因此，本實驗檢測健康個體、糖尿病無腎病變及糖尿性腎病變患者之TNF-α -308、IL-10 -1082、IL-10 -819和IL-10 -592基因多型性，分析其血清中生化數據、TNF-α、IL-10、MCP-1和尿中MCP-1之濃度表現，以探討糖尿性腎病變患者之細胞激素基因多型性與細胞激素表現之相關性。結果顯示三組檢體之TNF-α -308、IL-10 -1082和IL-10 -819基因多型性之表現均為異合子型，與糖尿病患者之腎病變發展並沒有關聯；糖尿病無腎病變患者及健康個體中IL-10 -592基因多型性為C/A之異合子型，然而糖尿性腎病變患者中IL-10 -592基因型C/A 、A/A及C/C分布分別為54.2%、29.2%及16.6%。此外，糖尿性腎病變患者血中TNF-α、MCP-1、TNF-α/IL-10以及尿液中MCP-1濃度顯著高於其他兩組，而BMCP-1/TNF-α則顯著偏低。研究結果也指出，帶有IL-10 -592 A/A異合子型之糖尿性腎病變患者，血中TNF-α、MCP-1和尿中MCP-1濃度表現高於其他兩基因型。實驗結果顯示，IL-10 -592基因多型性與糖尿性腎病變之發展有關。關鍵字：糖尿性腎病變；基因多型性；腫瘤壞死因子-α (TNF-α)；白細胞介素-10 (IL-10)；單核球趨化蛋白 (MCP-1) Diabetic nephropathy is a very common complication of diabetes mellitus. Mostly cytokines involved in these respective patients with hemodialysis are TNF-α, IL-2, IL-6 and IFN-γ. TNF-α mainly promotes the inflammation, induces apoptosis and regulates the secretions of other inflammatory mediators. MCP-1 is primarily produced by mesangial cells and tubular epithelial cells in kidney and mediates renal interstitial inflammation, tubular atrophy and interstitial fibrosis. IL-10 is an important component of the anti-inflammatory cytokine network in sepsis, suppressing gene expression and synthesis of proinflammatory cytokines. Gene polymorphisms of TNF-α and IL-10 are known to be related to the risk of death among patients with acute renal failure who require dialysis. The present study is to investigate the biochemistry parameter, gene polymorphisms of TNF-α -308 and IL-10 -1082, -819, -592 and their correlations to the protein expressions and blood and urine MCP-1 levels in subjects in diabetic nephropathy, diabetes mellitus and