腎積水后miRNA-210及其下游基因的表達(dá)變化
發(fā)布時間:2018-02-23 06:20
本文關(guān)鍵詞: 小鼠 腎積水 缺氧誘導(dǎo)因子-1α 血管內(nèi)皮生長因子 microRNA-210 UUO 出處:《南昌大學(xué)》2014年碩士論文 論文類型:學(xué)位論文
【摘要】:目的和意義: 腎積水是多種腎內(nèi)外因素作用于泌尿系后引起的一種常見的臨床表現(xiàn)。如果引起腎積水的因素不能得到及時解除,腎臟皮質(zhì)會因為受到尿液壓迫而引起腎組織的缺血缺氧,因此盡快解除引起腎積水的因素對于腎功能的保護(hù)有著極為重要的意義。研究發(fā)現(xiàn)新生血管的發(fā)生發(fā)展主要通過VEGF信號通路來發(fā)揮調(diào)控功能。最近研究報道發(fā)現(xiàn)miRNA可以調(diào)控血管新生,缺血缺氧后組織中HIF-1α表達(dá)上調(diào),某些miRNA表達(dá)也會發(fā)生顯著的改變。研究還提示miRNA-210這一作用可能是通過調(diào)控下游基因參與血管生成的信號通路并以此影響血管生成。 本研究通過制作小鼠單側(cè)腎積水病理模型,觀察小鼠腎積水后缺氧誘導(dǎo)因子-1α(HIF-1α)、血管內(nèi)皮生長因子(VEGF)、microRNA-210在不同時間點的的表達(dá)變化并探討其調(diào)控機制。 方法: 采用絲線結(jié)扎單側(cè)輸尿管的方法制備急性完全性單側(cè)腎積水病理模型(UUO模型),分為假手術(shù)對照組和單側(cè)腎積水組,于單側(cè)腎積水后2d、5d、9d、14d分別頸椎脫臼處死小鼠收集患腎。采用熒光實時定量PCR的方法檢測單側(cè)腎積水后患腎各個時間點HIF-1mRNA、VEGFmRNA及microRNA-210的表達(dá)變化,采用western-blot方法檢測單側(cè)腎積水后各時間點HIF-1α蛋白的表達(dá)變化趨勢。 結(jié)果: HIF-1αmRNA表達(dá)水平在腎積水后表達(dá)量逐漸上調(diào)直到處死該實驗動物(P均<0.05)。VEGFmRNA及microRNA-210表達(dá)水平在單側(cè)腎積水后2d升高并達(dá)到高峰,于單側(cè)腎積水后5d、9d、14d表達(dá)量逐漸下調(diào)(P均<0.05)。HIF-1α蛋白表達(dá)量逐漸上調(diào)。 結(jié)論: 實驗結(jié)果表明單側(cè)腎積水后患腎HIF-1αmRNA及蛋白表達(dá)逐步上調(diào),VEGFmRNA及microRNA-210表達(dá)出現(xiàn)一過性上調(diào),可能與單側(cè)腎積水后患腎皮質(zhì)被尿液壓迫,,機體對缺氧、缺血產(chǎn)生適應(yīng)性反應(yīng)有一定關(guān)系。
[Abstract]:Purpose and significance:
Hydronephrosis is a common clinical manifestation of renal function of various internal and external factors in the urinary system caused by hydronephrosis caused by factors. If not be lifted in time because of renal cortex caused by compression of urine kidney tissue ischemia and hypoxia, so as soon as possible to lift the protection factors to cause hydronephrosis and renal function has a very important. The study found that the development of new blood vessels mainly through the VEGF pathway to play a regulatory function. Recent studies suggest that miRNA can regulate angiogenesis, upregulation of HIF-1 expression after ischemia and hypoxia, some miRNA expression will also change significantly. This study also suggests a possible role of miRNA-210 signaling pathway is involved in blood vessel generated by the regulation of downstream genes and thus affect angiogenesis.
In this study, we made a pathological model of unilateral hydronephrosis in mice, and observed the expression changes of hypoxia inducible factor -1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF) and microRNA-210 at different time points after hydronephrosis in mice, and discussed the regulation mechanism.
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