本文選題：高尿酸血癥 + EMT��； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究背景持續(xù)的高尿酸血癥(Hyperuricemia,HUA)使尿酸鹽堆積引起腎臟病變,稱(chēng)尿酸性腎病。許多慢性腎病(Chronic kidney disease,CKD)有共同的病理過(guò)程一腎小管間質(zhì)纖維化(Renal Inierstitial Fibrosis,RIF),腎小管上皮間質(zhì)轉(zhuǎn)化(epithelial mesenchyml transition,EMT)被認(rèn)為是 RIF 的早期表現(xiàn)。腎小管 EMT即腎小管上皮細(xì)胞失去表型特征而獲得間質(zhì)細(xì)胞表型特征的過(guò)程。EMT受多種因素誘導(dǎo)和促發(fā),轉(zhuǎn)化生長(zhǎng)因子(TGF-β)是最為重要的誘導(dǎo)因子,在EMT參與胚胎發(fā)育、腫瘤轉(zhuǎn)移、器官纖維化中均有非常重要的作用。尿酸(Uricacid,UA)直接刺激腎小管上皮細(xì)胞,使E-cadherin的合成減少、a-SMA表達(dá)增加,腎小管發(fā)生EMT。此外,UA還通過(guò)泛素化增加了 E-cadherin的降解,導(dǎo)致腎小管上皮細(xì)胞的極性消失。黃嘌呤氧化酶抑制劑(Xanthine oxidase inhibitors,XOI)非布司他能降低UA水平,減輕CKD病情,但缺乏大規(guī)模前瞻性臨床試驗(yàn)證明。目的觀察HUA大鼠腎功能及腎臟結(jié)構(gòu)的變化,探討UA引起腎小管上皮EMT的可能機(jī)制。使用非布司他和苯溴馬隆片分別干預(yù)治療,觀察并比較兩藥對(duì)HUA大鼠腎小管上皮間質(zhì)轉(zhuǎn)化的影響,進(jìn)一步探討非布司他在預(yù)防腎纖維化中的作用。(1)SD大鼠隨機(jī)分為正常對(duì)照組(NC組)、HUA組、非布司他組(FX組)及苯溴馬隆組(BN組),每組12只。氧嗪酸鉀灌胃建立HUA模型。FX組及BN組在造模的同時(shí)給予非布司他(7.2mg/(kg.d))和苯溴馬隆(9mg/(kg.d))治療。(2)檢測(cè)大鼠血 UA、Scr、BUN、IL-6、Cys-c、TGF-β1、BMP-7 及尿蛋白的水平;HE及Masson染色觀察腎組織情況,免疫組化測(cè)定E-cadherin、a-SMA、CollageⅢ及 TGF-β1 的表達(dá)。結(jié)果與NC組對(duì)比,各組UA、Scr、BUN、IL-6、Cys-c及TGF-β1水平均升高,BMP-7水平下降,差異均有統(tǒng)計(jì)學(xué)意義(P0.05或P0.01);第4周時(shí),FX組 Cys-c、IL-6、TGF-β1 水平較 HUA 組明顯下降(P0.01);UA 與 IL-6、Cys-c及TGF-β1呈正相關(guān)關(guān)(r=0.908,P=0.000;r=0.759,P=0.000;r=0.850,P=0.000),與BMP-7呈負(fù)相關(guān)關(guān)系(r=-0.826,P=0.000)。HE染色顯示,非布司他治療明顯改善腎損傷;Masson染色提示HUA組腎纖維化程度大于其他三組(P0.01),FX組纖維化緩解優(yōu)于BN組;免疫組化檢測(cè)發(fā)現(xiàn),NC組腎組織不表達(dá)a-SMA,高表達(dá)E-cadherin;FX組與HUA組比較,a-SMA及CollageⅢ明顯減少(P0.01),E-cadherin表達(dá)增加(P0.01)。結(jié)論HUA引起腎小管EMT發(fā)生,腎小管上皮細(xì)胞的表型轉(zhuǎn)化是在腎間質(zhì)顯著纖維化前發(fā)生的;Cys-c較傳統(tǒng)的腎功能指標(biāo)更敏感,可作為早期尿酸性腎損傷的預(yù)測(cè)指標(biāo);非布司他有效地降低UA水平,減少I(mǎi)L-6/TGF-β1的表達(dá),增加BMP-7拮抗TGF-β1的作用,逆轉(zhuǎn)早期纖維化的發(fā)生。但非布司他對(duì)IL-6/TGF-β1及BMP-7/TGF-β1的具體調(diào)控機(jī)制需進(jìn)一步研究。
[Abstract]:Background: hyperuricemia and hyperuricemia (HUAA) cause renal disease caused by accumulation of uric acid, known as uric acid nephropathy. Many chronic kidney disease (CKD) have a common pathological process: renal tubulointerstitial fibrosis (RIF), epithelial mesenchyml transition (EMTT) is considered to be the early manifestation of RIF. Tubule EMT is the process of obtaining the phenotypic characteristics of interstitial cells due to the loss of phenotypic characteristics of renal tubular epithelial cells. TGF- 尾 is the most important inducing factor, and TGF- 尾 is the most important inducer in EMT, which is involved in embryonic development and tumor metastasis. Organ fibrosis plays a very important role. Uricacidy UAA directly stimulated renal tubule epithelial cells, which decreased the expression of E-cadherin and increased the expression of a-SMA in renal tubules. In addition, UA increased the degradation of E-cadherin through ubiquitization, resulting in the disappearance of the polarity of renal tubular epithelial cells. Xanthine oxidase inhibitors (XOI) can reduce UA level and alleviate the condition of CKD, but lack of large scale prospective clinical trials. Objective to observe the changes of renal function and renal structure in HUA rats and to explore the possible mechanism of renal tubular epithelial EMT induced by UA. To observe and compare the effects of the two drugs on renal tubule epithelial interstitial transformation in HUA rats. To further explore the role of fentinastar in the prevention of renal fibrosis, SD rats were randomly divided into normal control group (NC group), control group (n = 12), control group (n = 12) and group B (n = 12). HUA model was established by intragastric administration of potassium oxazinate. FX group and BN group were treated with non-busultadine 7.2mg / kg 路dl and benzbromarone 9 mg / kg 路dX).) the level of Scr-BUNIL-6 Cys-cTGF- 尾 1BMP-7 and urine protein were detected by HE staining and Masson staining. The expression of E-cadherina-SMA Collage 鈪，

本文編號(hào)：1924928