本文選題：睡眠呼吸暫停綜合征 + 慢性間歇性缺氧��； 參考：《福建醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的通過建立孕鼠及子代鼠的慢性間歇性缺氧（chronic intermittent hypoxia,CIH）模型，探討CIH對子代鼠動脈粥樣硬化病變所造成的影響及其中所涉及的可能的機制。 方法SD孕鼠16只，于孕第7天隨機分為常氧組和CIH兩大組。待分娩后，每只孕鼠的子代中隨機抽取2只雄性仔鼠喂養(yǎng)至4周齡，根據(jù)母代是否經(jīng)歷CIH,這些子代同樣被分為常氧組和CIH兩大組，每大組子代鼠再進一步隨機分為常氧組和CIH組，最終得到以下4個組別，每組8只：(1)宮內(nèi)常氧+子代常氧組（即對照組）；（2）宮內(nèi)常氧+子代CIH組；（3）宮內(nèi)CIH+子代常氧；（4）宮內(nèi)CIH+子代CIH組。子代CIH組再次進行間歇性缺氧，持續(xù)12周。CIH結(jié)束后取子代鼠胸腹主動脈標(biāo)本，制做病理切片, HE染色光學(xué)顯微鏡下觀察血管標(biāo)本病理形態(tài)，對比各組動脈內(nèi)膜、中膜厚度。然后用western-blot法測定子代鼠動脈核轉(zhuǎn)錄因子（nuclear factor-κBp65， NF-κBp65）、小窩蛋白-1（Caveolin-1）、細胞外信號調(diào)節(jié)激酶1/2（extracellular signal-regulated kinase1/2，ERK1/2）磷酸化細胞外信號調(diào)節(jié)激酶1/2（phosphorylated extracellularsignal-regulated kinase1/2,p-ERK1/2）蛋白表達水平。 結(jié)果（1）CIH可引起子代大鼠動脈內(nèi)膜增厚：宮內(nèi)CIH+子代常氧組（3.800±0.543μm）、宮內(nèi)CIH+子代CIH組（6.440±0.977μm）、宮內(nèi)常氧+子代CIH組（5.692±0.708μm）與對照組（1.555±0.259μm）相比，差異有統(tǒng)計學(xué)意義（P＜0.001）。而CIH對中膜的改變無統(tǒng)計學(xué)意義（P=0.974）。（2）CIH可以促進子代大鼠NF-κBp65蛋白表達增加：宮內(nèi)CIH+子代常氧組（0.020±0.002）、宮內(nèi)CIH+子代CIH組（0.024±0.002）、宮內(nèi)常氧+子代CIH組（0.022±0.001）與對照組（0.013±0.001）相比，差異有統(tǒng)計學(xué)意義（P＜0.001）。（3）CIH可以促進子代大鼠Caveolin-1蛋白表達增加：宮內(nèi)CIH+子代常氧組（0.348±0.027）、宮內(nèi)CIH+子代CIH組（0.380±0.027）、宮內(nèi)常氧+子代CIH組（0.361±0.037）與對照組（0.230±0.014）相比，差異有統(tǒng)計學(xué)意義（P＜0.01）。（4）CIH對子代大鼠ERK1/2蛋白的表達改變無統(tǒng)計學(xué)差異（P=0.998），而使得p-ERK1/2蛋白表達減少：宮內(nèi)CIH+子代常氧組（1.530±0.272）、宮內(nèi)CIH+子代CIH組（0.802±0.135）、宮內(nèi)常氧+子代CIH組（1.260±0.208）與對照組（2.303±0.176）相比，差異有統(tǒng)計學(xué)意義（P＜0.01）。(5)宮內(nèi)CIH與子代CIH能協(xié)同加重上述各觀察指標(biāo)變化(P＜0.001或P＜0.05)。（6）各組NF-κBp65與Caveolin-1蛋白相對表達量存在正相關(guān)關(guān)系（r=0.848，P＜0.001）。各組Caveolin-1與p-ERK1/2蛋白相對表達量存在負相關(guān)關(guān)系（r=0.-810，P＜0.001）。各組NF-κBp65蛋白相對表達量與動脈內(nèi)膜厚度存在正相關(guān)關(guān)系（r=0.880，P＜0.001）。各組Caveolin-1蛋白相對表達量與動脈內(nèi)膜厚度存在正相關(guān)關(guān)系（r=0.811，，P＜0.001）。各組p-ERK1/2蛋白相對表達量與動脈內(nèi)膜厚度存在負相關(guān)關(guān)系（r=-0.877，P＜0.001）。 結(jié)論1、宮內(nèi)CIH可以誘發(fā)子代鼠出現(xiàn)動脈粥樣硬化早期病變；2、子代CIH可加重經(jīng)歷宮內(nèi)CIH所誘導(dǎo)的動脈硬化的嚴(yán)重程度，兩者具有協(xié)同作用。3、NF-κBp65/Caveolin-1/p-ERK1/2信號通路可能是CIH所誘導(dǎo)的動脈粥樣硬化中的重要機制之一。
[Abstract]:Objective To establish a model of chronic intermittent hypoxia ( CIH ) in pregnant rats and offspring rats .

Methods Sixteen male pregnant rats were randomly divided into two groups : normal oxygen group and CIH group on the 7th day of pregnancy . The offspring of each pregnant rat were randomly divided into two groups : normal oxygen group and CIH group . The offspring of each group were divided into two groups : normal oxygen group and CIH group .
( 2 ) The normal oxygen + filial generation CIH group in the uterus ;
( 3 ) CIH + subnormal oxygen in the uterus ;
( 4 ) In the CIH + filial generation CIH group , the expression level of extracellular signal - regulated kinase1 / 2 , p - 1 / 2 protein was measured by western - blot . The expression level of extracellular signal - regulated kinase1 / 2 , p - 1 / 2 protein was measured by Western - blot .

Results ( 1 ) CIH could increase the expression of Caveolin - 1 protein in filial rats ( P < 0 . 001 ) . There was a negative correlation between Caveolin - 1 and p - 1 / 2 protein expression in each group ( r = 0.- 810 , P < 0.001 ) . There was positive correlation between the relative expression of NF - 魏B and the thickness of the intima . There was positive correlation between the relative expression of Caveolin - 1 and the thickness of intima . There was a negative correlation between the relative expression of p - 1 / 2 protein in each group and the thickness of the intima ( r = - 0.877 , P < 0.001 ) .

Conclusion 1 . CIH could induce early atherosclerotic lesion in offspring rats .
2 . Subgeneration CIH can aggravate the severity of atherosclerosis induced by CIH in the uterus . Both of them have a synergistic effect . 3 . NF - 魏B P65 / Caveolin - 1 / p - 1 / 2 signaling pathway may be one of the important mechanisms in CIH - induced atherosclerosis .

【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R766

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相關(guān)期刊論文 前2條

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