引用本文:查克岚1,李家富1,曾 瑜2.SDF- 1/CXCR 4在槲皮素抗ApoE-/-小鼠动脉粥样硬化形成过程中的作用[J].重庆医科大学学报,,():
SDF- 1/CXCR 4在槲皮素抗ApoE-/-小鼠动脉粥样硬化形成过程中的作用
Role of SDF- 1/CXCR 4 in the process of quercetin against atherosclerosis in ApoE-/- mice
DOI:
中文关键词:  槲皮素  动脉粥样硬化  基质细胞衍生因子-1  基质细胞衍生因子受体
英文关键词:quercetin  atherosclerosis  stromal derived factor-1  CXCR 4
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作者单位
查克岚1,李家富1,曾 瑜2 1.四川省泸州医学院附属医院心血管内科泸州 6460002.重庆市第七人民医院心内科重庆 400039 
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中文摘要:
      目的:探讨槲皮素对ApoE-/-小鼠动脉粥样硬化(arteriosclerosis,AS)形成及基质细胞衍生因子-1(stromal derived factor-1,SDF- 1)及其特异性受体CXCR 4表达的影响,为槲皮素抗动脉粥样硬化提供实验依据。方法:40只6周龄的ApoE-/-小鼠随机分为:正常对照组、模型对照组和实验组(槲皮素低、中、高剂量组),于给药后第10、20周取材, HE染色观察动脉粥样硬化病变情况; ELISA法、免疫组织化学技术及real-time PCR检测SDF- 1和CXCR 4的蛋白和基因表达情况。结果:1、HE染色发现正常组无粥样斑块形成;实验组与高脂饮食组相比动脉粥样斑块病变明显减轻。2、免疫组化结果显示相同时间点比较,正常对照组:SDF-1主要表达于内皮细胞和平滑肌细胞,CXCR4主要表达于内皮细胞,但细胞着色浅,表达量少;模型对照组:平滑肌细胞以及泡沫细胞呈深棕黄色,显示SDF-1和CXCR4有大量表达;槲皮素组:高中低剂量的3个实验组与模型对照组比较,细胞着色较浅,表达量均有减少(P=0.010);与正常对照组比较,低剂量组、中剂量组有统计学差异(P=0.000)。不同时间点比较,SDF-1在模型对照组的表达量随时间延长而增加(P=0.000)。3、ELISA检测血清中SDF-1和CXCR4水平,real-time PCR检测SDF-1和CXCR4的 mRNA基因表达结果:在相同时间点比较,SDF-1及CXCR4在模型对照组中表达最高(与其余各组比较P=0.000),正常对照组表达最低,槲皮素组介于两者之间,且随着药物剂量的增加SDF-1和CXCR4表达量进行性下降,尤其是CXCR4在高剂量组与正常对照组比较无统计学差异(P>0.05);不同时间点相同组比较,模型对照组的SDF-1和CXCR4均随时间延长而增加(P=0.00),槲皮素组和正常对照组无显著的时间依赖性。结论: 1、SDF- 1/CXCR 4可能促进血管平滑肌细胞增殖以及迁移至内膜,从而使内膜增厚和泡沫细胞形成,导致粥样斑块形成。2、槲皮素可能通过抑制SDF- 1与 CXCR 4的表达从而抑制ApoE-/-小鼠动脉粥样硬化形成。
英文摘要:
      Objective: To explore quercetin on ApoE - / - mice atherosclerosis formation and expression of stromal derived factor-1(SDF- 1)/CXCR4, and to provide experimental basis for anti- atherosclerosis of the quercetin. Methods: Forty 6-week-old ApoE-/- mice were divided randomly into four groups: normal control, model group and experimental group (with low-dose, mid-dose and high-dose quercetin) and were randomly are sacrificed at the time of the 10 th week and 20 th week after the administration of the drugs respectively. SDF-1 and CXCR 4 protein and gene expressions were measured by ELISA, immunohistochemical technique and real-time PCR. Results: 1. HE staining demonstrated no plaque formation in normal group and lighter plaque formation in model group than in high-fat diet group. 2. According to immunohistochemical results at the same time points: in normal group, SDF-1 was mainly existed in endothelial cells and smooth muscle cells and CXCR4 mainly existed in endothelial cells; the expression was few and the staining was light ; in model group, there were abundant expression of SDF-1 and CXCR4 in smooth muscle cells and foam cells, appearing in deep brown-yellow color; in experiment group , expressions of SDF-1 and CXCR4 were decreased in all three subgroups than in model group(P=0.010). Statistical differences were found between low-dose and mid-dose groups and normal group (P=0.000). According to immunohistochemical results at the different time points, expression of SDF-1 in model group increased in time-dependent manner (P=0.000). 3. ELISA results of SDF-1 and CXCR4 level in serum and real-time PCR results of SDF-1 and CXCR4 mRNA expression at the same time points: expression of SDF-1 and CXCR4 was the highest in model group (compared with other groups, P =0.000) and was the lowest in normal group. The expression of SDF-1 and CXCR4 progressively decreased with the increase of the dose of quercetin, especially there was no statistical difference in CXCR4 between high-dose group normal group (P>0.05). At different time points, SDF-1 and CXCR4 in model group increased in time-dependent manner (P=0.00). But no apparent time dependence occurred in experiment group and normal group. Conclusion: SDF- 1/CXCR 4 may promote vascular smooth muscle cell proliferation and migration to the intima, so as to thicken the intima, form foam cell and lead to plaque formation. Quercetin may inhibit the expression of SDF-1 and CXCR4 and ApoE -/- mice atherosclerosis formation, which may be one of the mechanisms of its anti- atherosclerosis.
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