敲除清道夫受体A iv/一七基因对小鼠氧化型低密度脂蛋白组织分布和清除的影响
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国家自然科学基金(30670979);;广东省自然科学基金(5001206)资助


The Impact of Scavenger Receptor Class A Type Ⅰ/Ⅱ on Distribution and Clearance of Oxidative Low Density Lipopprotein in Mice
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    摘要:

    目的应用清道夫受体A iv/一七基因敲除小鼠及其野生对照小鼠,观察在正常饮食和高脂饮食情况下,清道夫受体A iv/一七对小鼠氧化型低密度脂蛋白分布和清除的影响。方法用Southernblot和免疫组织化学法鉴定实验小鼠清道夫受体A iv/一七DNA和蛋白的表达。将2月龄雄性野生对照小鼠和清道夫受体A iv/一七基因敲除小鼠各50只随机分为4组:清道夫受体A iv/一七基因敲除小鼠和野生对照小鼠各38只,给予高脂饮食(常规饲料加15%油脂和1.25%胆固醇)8周,观察实验前后血清总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、载脂蛋白A、载脂蛋白B及血肌酐等水平的变化;清道夫受体A iv/一七基因敲除小鼠和野生对照小鼠各12只,高脂饮食3天后从尾静脉注射125I标记的氧化型低密度脂蛋白,于10min、1、3和6h获取血液、心脏、肝脏、脾脏、肺脏、肾脏、胃、肠、脂肪和肌肉等标本,分别称取质量并用γ射线计数仪检测其放射性强度。结果正常饮食下,清道夫受体A iv/一七基因敲除小鼠和野生对照小鼠血脂水平接近;高脂饮食下两组小鼠血脂水平均明显升高,但清道夫受体A iv/一七基因敲除小鼠血浆低密度脂蛋白水平明显高于野生对照小鼠;清道夫受体A iv/一七基因敲除小鼠在注射125I标记的氧化型低密度脂蛋白10min后的清除率明显低于野生对照小鼠,注射125I标记的氧化型低密度脂蛋白6h后其主要分布于肝脏,在心脏和肾脏也有高分布;高脂饮食条件下,敲除清道夫受体A iv/一七基因对经尾静脉注射的125I标记的氧化型低密度脂蛋白在体内的分布不同于野生对照小鼠。结论敲除清道夫受体A iv/一七后,小鼠脂质代谢的调节能力受到损伤,机体对血液中氧化型低密度脂蛋白的清除能力下降,组织细胞对氧化型低密度脂蛋白的摄取减少,血低密度脂蛋白水平升高。

    Abstract:

    Aim To investigate the impact of scavenger receptor class A type Ⅰ/Ⅱ(SR A iv/一七)on the clearance and distribution of oxidized low density lipoprotein(LDL)of mouse under the condition of normal diet and high lipid diet.Methods Each one of SR A iv/一七gene knock out(SR-/-)mice and wild control(SR +/+)mice was randomly picked from each strip to be identified by Southern blot and immunohistochemistry.And then,50 SR-/-and 50 SR +/+ 2-month-old male,weighting about 25 g mice were divided into 4 groups:38 SR-/-mice and 38 SR +/+ mice were fed with high lipid diet(normal food with 15% fatty and 1.25% cholesterol)for 8 weeks.The serum levels of creatinine(Cr),triglyceride(TG),total cholesterol(TC),LDL,high density lipoprotein(HDL),apolipoprotein A(apo A),apolipoprotein B(apo B)and body weight(BW)were measured at 8 weeks.12 SR-/-mice and 12 SR +/+ mice were intravenous injected 125 I labeled ox-LDL(125I-ox-LDL)through their tail veins after 3 days high lipid diet.10 min and 3 h after injection,blood samples were harvested from 6 mice by cutting the tail,1 h and 6 h after injection,blood samples were harvested again respectively from eye veins.After humanly killed,the heart,liver,spleen,lung,kidney,stomach,intestines,fat as well as muscle samples were harvested and carefully weighted after circulation was perfused with 5 mL PBS at 4℃.The radiation activity was determined in a multiple-channel gamma counter.Results No significant difference of serum levels of lipid were found between SR-/-and SR +/+ mice fed with

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王文健,余学清,史伟,梁馨苓,窦献蕊,陈文芳,李晓艳,刘双信,黄锋先.敲除清道夫受体A iv/一七基因对小鼠氧化型低密度脂蛋白组织分布和清除的影响[J].中国动脉硬化杂志,2007,15(2):85~89.

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  • 收稿日期:2006-10-16
  • 最后修改日期:2007-02-01
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