慢性间歇性缺氧对孕鼠子代鼠动脉粥样硬化病变及Caveolin-1的影响

发布时间：2018-04-29 00:14

本文选题：睡眠呼吸暂停综合征 + 慢性间歇性缺氧　；参考：《福建医科大学》2013年硕士论文

【摘要】：目的通过建立孕鼠及子代鼠的慢性间歇性缺氧（chronic intermittent hypoxia,CIH）模型，探讨CIH对子代鼠动脉粥样硬化病变所造成的影响及其中所涉及的可能的机制。方法SD孕鼠16只，于孕第7天随机分为常氧组和CIH两大组。待分娩后，每只孕鼠的子代中随机抽取2只雄性仔鼠喂养至4周龄，根据母代是否经历CIH,这些子代同样被分为常氧组和CIH两大组，每大组子代鼠再进一步随机分为常氧组和CIH组，最终得到以下4个组别，每组8只：(1)宫内常氧+子代常氧组（即对照组）；（2）宫内常氧+子代CIH组；（3）宫内CIH+子代常氧；（4）宫内CIH+子代CIH组。子代CIH组再次进行间歇性缺氧，持续12周。CIH结束后取子代鼠胸腹主动脉标本，制做病理切片, HE染色光学显微镜下观察血管标本病理形态，对比各组动脉内膜、中膜厚度。然后用western-blot法测定子代鼠动脉核转录因子（nuclear factor-κBp65， NF-κBp65）、小窝蛋白-1（Caveolin-1）、细胞外信号调节激酶1/2（extracellular signal-regulated kinase1/2，ERK1/2）磷酸化细胞外信号调节激酶1/2（phosphorylated extracellularsignal-regulated kinase1/2,p-ERK1/2）蛋白表达水平。结果（1）CIH可引起子代大鼠动脉内膜增厚：宫内CIH+子代常氧组（3.800±0.543μm）、宫内CIH+子代CIH组（6.440±0.977μm）、宫内常氧+子代CIH组（5.692±0.708μm）与对照组（1.555±0.259μm）相比，差异有统计学意义（P＜0.001）。而CIH对中膜的改变无统计学意义（P=0.974）。（2）CIH可以促进子代大鼠NF-κBp65蛋白表达增加：宫内CIH+子代常氧组（0.020±0.002）、宫内CIH+子代CIH组（0.024±0.002）、宫内常氧+子代CIH组（0.022±0.001）与对照组（0.013±0.001）相比，差异有统计学意义（P＜0.001）。（3）CIH可以促进子代大鼠Caveolin-1蛋白表达增加：宫内CIH+子代常氧组（0.348±0.027）、宫内CIH+子代CIH组（0.380±0.027）、宫内常氧+子代CIH组（0.361±0.037）与对照组（0.230±0.014）相比，差异有统计学意义（P＜0.01）。（4）CIH对子代大鼠ERK1/2蛋白的表达改变无统计学差异（P=0.998），而使得p-ERK1/2蛋白表达减少：宫内CIH+子代常氧组（1.530±0.272）、宫内CIH+子代CIH组（0.802±0.135）、宫内常氧+子代CIH组（1.260±0.208）与对照组（2.303±0.176）相比，差异有统计学意义（P＜0.01）。(5)宫内CIH与子代CIH能协同加重上述各观察指标变化(P＜0.001或P＜0.05)。（6）各组NF-κBp65与Caveolin-1蛋白相对表达量存在正相关关系（r=0.848，P＜0.001）。各组Caveolin-1与p-ERK1/2蛋白相对表达量存在负相关关系（r=0.-810，P＜0.001）。各组NF-κBp65蛋白相对表达量与动脉内膜厚度存在正相关关系（r=0.880，P＜0.001）。各组Caveolin-1蛋白相对表达量与动脉内膜厚度存在正相关关系（r=0.811，，P＜0.001）。各组p-ERK1/2蛋白相对表达量与动脉内膜厚度存在负相关关系（r=-0.877，P＜0.001）。结论1、宫内CIH可以诱发子代鼠出现动脉粥样硬化早期病变；2、子代CIH可加重经历宫内CIH所诱导的动脉硬化的严重程度，两者具有协同作用。3、NF-κBp65/Caveolin-1/p-ERK1/2信号通路可能是CIH所诱导的动脉粥样硬化中的重要机制之一。
[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 .

【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R766

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