Valsartan合併Aliskiren使用可有效改善由單側輸尿管阻塞所造成的腎臟纖維化

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Title:	Valsartan合併Aliskiren使用可有效改善由單側輸尿管阻塞所造成的腎臟纖維化 A reduction of unilateral ureteral obstruction induced renal fibrosis by a therapy combined valsartan with aliskiren
Authors:	巫文平;Wen-Pyng Wu
Contributors:	醫學院臨床醫學研究所碩士班
Keywords:	腎素直接抑制劑;血管張力素受體阻斷劑;腎臟纖維化;單側輸尿管阻塞;direct renin inhibitor;angiotensin II receptor blocker;renal fibrosis;unilateral ureteral obstruction
Date:	2010
Issue Date:	2010-09-29 12:17:09 (UTC+8)
Abstract:	腎臟纖維化(Renal fibrosis)在慢性腎臟病中是一個重要的病理變化。大鼠的單側輸尿管阻塞 (Unilateral Ureteric Obstruction, UUO）是表現間質炎性細胞浸潤和腎小管擴張並造成阻塞腎臟的腎小管間質纖維化的一個動物模式。以血管張力素轉換酶抑制劑 (angiotensin converting enzyme inhibitor, ACEI) 、血管張力素受體阻斷劑 (angiotensin receptor blocker, ARB)或腎素直接抑制劑 (direct renin inhibitor, DRI) 阻斷腎素-血管張力素-醛固酮系統系統(renin-angiotensin-aldosterone system )或在糖尿病腎病變中已證實有保護腎臟的作用。在這項研究中，我們經由病理檢查、免疫組織化學特殊染色分析(immunohistochemical analysis)、西方墨點分析(Western blot)、反轉錄聚合酶連鎖反應(reverse transcription-PCR) 和血液的檢測來評估valsartan與aliskiren合併治療對UUO所誘導的腎纖維化的療效。我們分別在UUO 後第七天和第十四天做評估。在這兩個不同天數的大分組中，又細分有五個小組，分別是假性手術組、UUO 手術加安慰劑組、valsartan 治療組、aliskiren治療組及合併治療組。我們觀察到合併治療或單獨治療都可顯著減少阻塞的腎臟的重量及長度，也就是改善水腎的程度。特別的是，合併治療具有最佳的效果。合併治療也比單獨使用aliskiren 或valsartan明顯減弱 UUO 所造成的腎小管擴張、腎間質容積、腎間質膠原蛋白沉積、α-平滑肌肌動蛋白的增加、ERK 1/2 的活化、單核細胞卅巨噬細胞的浸潤、snail-1 和β1 型轉化生長因子（TGF-β1）的訊息核糖核酸（m-RNA）的表現。總結來說，合併治療明顯地減弱大鼠UUO 所導致的腎纖維化中的腎小管間質損傷，而且比 aliskiren 或valsartan單一治療效果更好。 Renal fibrosis is an important pathologic change in chronic kidney disease. Unilateral ureteral obstruction (UUO)　in the rodent is a model exhibiting interstitial inflammatory cell infiltration and tubular dilatation followed by tubulointerstitial fibrosis of the obstructed kidney. The blockade of the renin-angiotensin-aldosterone system with either angiotensin converting enzyme inhibitor, angiotensin receptor blocker or direct renin inhibitor has renoprotective effect in diabetic nephropathy. In this study, we investigate the effect of a therapy combined aliskiren with valsartan on UUO-induced renal fibrosis by the pathologic examination, Western blot and reverse transcriptase PCR. Point counting method was used for scores of interstitial volume, interstitial collagen deposition, interstitial α-SMA and tubular dilatation to evaluate degree of renal fibrosis. We observed that the combination therapy or each alone all significantly blunted the degree of hydronephrosis determined by the increase of weight and length of the obstructed kidney. Specially, the combination therapy has the best renoprotective effect. The combination therapy also attenuated UUO related increases on the scores of tubular dilatation, interstitial volume, interstitial collagen deposition, α-smooth
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