肝X受体激动剂对高脂载脂蛋白E基因缺陷小鼠动脉壁一氧化氮合酶、增殖细胞核抗原和纤溶酶原激活物抑制剂1表达的影响
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The Effects of Liver X Receptor Agonists on the Expressions of Nitric Oxide Synthase,Proliferating Cell Nuclear Antigen and Plasminogen Activator Inhibitor-1 in the Artery of Apolipoprotein E-Deficient Mice
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    摘要:

    目的研究肝X受体激动剂3β-羟基-5α,6α-环氧胆烷酸甲酯和T-0901317对高脂载脂蛋白E基因缺陷小鼠动脉壁一氧化氮合酶、增殖细胞核抗原、纤溶酶原激活物抑制剂1表达的影响。方法以高脂饲养载脂蛋白E基因缺陷小鼠为动脉粥样硬化模型,分为无药对照组、3β-羟基-5α,6α-环氧胆烷酸甲酯干预组[10 mg/(kg.d)]和T-0901317干预组[10 mg/(kg.d)],每组6只小鼠,灌胃6周。用免疫组织化学SP法检测主动脉壁中诱导型一氧化氮合酶、内皮型一氧化氮合酶、增殖细胞核抗原、纤溶酶原激活物抑制剂1蛋白的表达。结果药物干预的两组主动脉壁中诱导型一氧化氮合酶的表达均显著低于对照组(p<0.01),而血管内皮细胞中内皮型一氧化氮合酶的表达均显著高于对照组(p<0.01)。各组增殖细胞核抗原和纤溶酶原激活物抑制剂1的表达无显著性差异(p<0.05)。结论肝X受体激动剂3β-羟基-5α,6α-环氧胆烷酸甲酯和T-0901317均可促进血管内皮细胞中内皮型一氧化氮合酶的表达,抑制动脉壁中诱导型一氧化氮合酶的表达。提示肝X受体激动剂还可通过调脂以外的其它途径,如抑制炎症反应和保护内皮功能等方面,发挥其抗动脉粥样硬化作用。

    Abstract:

    Aim To study the effects of methyl 3β-hydroxy-5α,6α-epoxycholanate(MHEC) and T-0901317 on the expressions of nitric oxide synthase(NOS),proliferating cell nuclear antigen(PCNA) and plasminogen activator inhibitor-1(PAI1) in the artery wall. Methods Apolipoprotein E-deficient(ApoE~(-/-)) mice were fed with an atherogenic diet,two types of liver X receptor(LXR) agonists(T-0901317 and MHEC) were orally administered daily at dose of 10 mg/kg for 6 weeks.SP immunohistochemistry analysis was performed to detect the expressions of induced NOS(iNOS),endothelial NOS(eNOS),PCNA and PAI-1 in the aortic atherosclerotic lesions. Results The expression of iNOS in the aortic wall was decreased in MHEC group and T-0901317 group compared with control group(p<0.01);while the expression of eNOS in the endothelium was increased significantly(p<0.01).The expressions of PCNA and PAI-1 in each group didn't differ markedly(p<0.05). Conclusions MHEC and T-0901317 could induce the expression of eNOS in the endothelium,while the expression of iNOS in the aortic wall was partly inhibited.This suggests that LXR agonists may take its anti-atherosclerosis role by inhibiting the inflammation in the artery wall and protecting the endothelial function.

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胡厚源,颜伟,周林.肝X受体激动剂对高脂载脂蛋白E基因缺陷小鼠动脉壁一氧化氮合酶、增殖细胞核抗原和纤溶酶原激活物抑制剂1表达的影响[J].中国动脉硬化杂志,2006,14(6):511~513.

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  • 收稿日期:2005-09-01
  • 最后修改日期:2006-04-27
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