中药虎杖和山楂提取物对载脂蛋白E基因敲除小鼠巨噬细胞PPARγ、ABCA1及CD36 mRNA表达的影响
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高等学校博士学科点专项科研基金(20060441002)


Effect on PPARγ,ABCA1 and CD36 mRNA in Macrophage of Apoprotein E Knock Out Mice with Extractive of Giant Knotweed Rhizome and Hawthorn
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    摘要:

    目的观察中药虎杖、山楂配伍对载脂蛋白E基因敲除小鼠巨噬细胞源性泡沫细胞内过氧化体增殖物激活型受体γ、三磷酸腺苷结合盒转运子A1及CD36 mRNA表达的影响,从基因水平探讨虎杖和山楂配伍对动脉粥样硬化泡沫细胞形成的干预机制。方法培养载脂蛋白E基因敲除小鼠腹腔巨噬细胞,分为空白组、虎杖苷组、山楂提取物组、虎杖苷+山楂提取物组、洛伐他汀组、罗格列酮组及模型组。除空白组外,其他各组均同时加入氧化型低密度脂蛋白及脂多糖。各组细胞在培养箱内共孵育(泡沫化)2天,以逆转录聚合酶链反应法检测0 h、24 h和48 h各组细胞内过氧化体增殖物激活型受体γ、三磷酸腺苷结合盒转运子A1及CD36的mRNA表达。结果与空白组比较,干预24 h和48 h后,模型组及各用药组三个指标的表达均显著增高(P<0.01);与模型组比较,干预24 h后,虎杖苷+山楂提取物组和罗格列酮组过氧化体增殖物激活型受体γmRNA表达显著增高,虎杖苷组、虎杖苷+山楂提取物组和罗格列酮组三磷酸腺苷结合盒转运子A1 mRNA表达显著增高(P<0.05或P<0.01),各用药组CD36 mRNA表达无显著差异(P>0.05);干预48 h后,各用药组过氧化体增殖物激活型受体γ和三磷酸腺苷结合盒转运子A1 mRNA表达均显著增高,CD36 mRNA表达显著降低,且虎杖苷+山楂提取物组优于虎杖苷组、山楂提取物组及洛伐他汀组(P<0.05或P<0.01)。结论虎杖和山楂配伍可能具有与罗格列酮相似的过氧化体增殖物激活型受体γ激动作用,通过上调载脂蛋白E基因敲除小鼠巨噬细胞过氧化体增殖物激活型受体γ和三磷酸腺苷结合盒转运子A1 mRNA表达、下调CD36 mRNA表达的调控途径显著抑制巨噬细胞泡沫化过程,阻止动脉粥样硬化进程。

    Abstract:

    Aim To observe changes of peroxisome proliferator activated receptor γ(PPARγ) mRNA,ATP-binding cassette transporter A1(ABCA1) mRNA and CD36 mRNA in foam cells which come from the peritoneal macrophage of apolipoprotein E knock out mice with giant knotweed rhizome,hawthorn and both of them,and discuss possible mechanism of anti-atherosclerosis on gene level. Methods ApolipoproteinE knock out mice peritoneal macrophage were incubated and divided into seven groups: blank group,polydatin group,extractive of hawthorn group,polydatin and extractive of hawthorn group,Lovastatin group,Rosiglitazone group and model group.Except for blank group,all other groups were added with oxidative low density lipoprotein and lipopolysaccharide.The course of incubation was 48 hours. Intracellular PPARγ mRNA,ABCA1 mRNA and CD36 mRNA of all groups were detected at 0 hour,24 hours and 48 hours respectively by method of RT-PCR. Results Compared with the blank group,above three indexes of the model group and all medicine groups increased obviously after they were induced for 24 or 48 hours(P<0.01).Compared with the model group,PPARγ mRNA of the polydatin and extractive of hawthorn group and the rosiglitazone group all increased obviously,ABCA1 mRNA of the polydatin group,the polydatin and extractive of hawthorn group and the rosiglitazone group all increased obviously(P<0.05 or P<0.01),and CD36 mRNA of all medicine groups had no obvious difference after they were treated for 24 hours(P>0.05).Compared with the model group,PPARγ mRNA and ABCA1 mRNA of all medicine groups increased obviously,CD36 mRNA of them decreased obviously after they were treated for 48 hours,moreover,the polydatin and extractive of hawthorn group was superior to the polydatin group,the extractive of hawthorn group and the lovastatin group(P<0.05 or P<0.01). Conclusions The compatibility of giant knotweed rhizome and hawthorn may have similar agitating effect on PPARγ with rosiglitazone.It can inhibit macrophages foaming and prevent formation of atherosclerosis through up-regulating PPARγ mRNA and ABCA1 mRNA,and down-regulating CD36 mRNA of apolipoprotein E knock out mice.

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刘美霞,张文高,刘龙涛.中药虎杖和山楂提取物对载脂蛋白E基因敲除小鼠巨噬细胞PPARγ、ABCA1及CD36 mRNA表达的影响[J].中国动脉硬化杂志,2009,17(11):902~906.

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  • 收稿日期:2009-09-22
  • 最后修改日期:2009-11-02
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