单核细胞趋化蛋白-1在兔食饵性动脉粥样硬化病变中的表达
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国家自然科学基金


Expression of Monocyte Chemoattractant Protein-1 in Dietary AtheroscleroticLesions in Rabbits
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    摘要:

    为了探讨单核细胞趋化蛋白-1(monocytechemoattractant protein-1,MCP-1)在动脉粥样硬化病变中的表达情况,以含胆固醇饲料复制家兔高脂血症和动脉粥样硬化模型。用Y32P末端标记的单核细胞趋化蛋白-1寡核苷酸探针检测斑块组织中单核细胞趋化蛋白-1mRAN的表达,夹心酶联免疫吸附法检测培养的斑块平滑肌细胞条件培养基中单核细胞趋化蛋白-1含量,免疫组织化学法观察斑块组织细胞中单核细胞趋化蛋白-1的表达。结果发现,动脉粥样硬化病变组织表达单核细胞趋化蛋白-1mRNA的积分光密度值(4.15)为对照组(0.38)的10.7倍。培养的斑块平滑肌细胞条件培养基中单核细胞趋化蛋白-1含量(10.0±0.8g/L)明显高于正常平滑肌细胞条件培养基(7.0±0.7g/L)和非条件培养基(6.4±0.7g/L),差异有极显著性意义(P<0.01)。免疫组织化学发现,斑块中的内皮细胞、巨噬细胞源泡沫细胞和增殖的平滑肌细胞均不同程度地表达单核细胞趋化蛋白-1,以巨噬细胞源泡沫细胞表达最强。此结果提示在高脂血症时,参与动脉粥样硬化斑块形成的细胞处于相当活跃状态,均能产生和分泌单核细胞趋化蛋白-1。

    Abstract:

    Aim To understand the monocyte chemoattractantprotein-1 (MCP-1 ) expression by the cells in dietaryatherosclerotic lesions in rabbits. .Methods The male 4~6 week old Japanese 1p rab-bits were fed on cholesterol to develop a hyperlipidemiaand atherosclerosis model. The MCP-1 mRNA ex-pression in the plaques was examined by dot blot anal-ysis using a probe of P-end-labeled 35-mer oligonu-cleotide of MCP-1. Meanwhile, the MCP-1 in themedia conditioned by cultured SMCs from theatherosclerotic lesions was determined by using sand-wich ELISA. Immunohistochemically, the expres-sion of MCP-1 in various cells in the plaques was ex-amined using a rabbit anti-MCP-1 polyclonal antibody,and to recognize the cells in the plaques, several anti-bodies including factor Ⅶ related antigen, a1-antit-rypsin and a-smooth muscle actin were used.Results Dot blot analysis showed that after hybridiza-tion of the RNA with the probe, the integral opticaldensity value (4. 1 5 ) of the autoradiographic pictures ofthe dots from the atherosclerotic lesions was 10. 7times the controls(0. 38). The MCP-1 content in themedia conditioned by cultured SMCs from theatherosclerotic lesions , asthe ELISA showed,was significantly higher than thatof the normal SMC conditioned media (7. 0±0. 7 g/L) and unconditioned medium (6.4 ±0. 7 g/L) (P<0. 01 ). Immunohistochemically, endothelial cells,macrophage derived foam cells and SMCs in theplaques were positively stained with anti-MCP-1 anti-body in varying degrees. Of the three cell types, themacrophage derived foam cells showed the strongestimmunostaining.Conclusion Under hyperlipidemic condition, theartery wall cells which participate in the developmentof atherosclerotic plaques were in full activity, andproduced and secreted MCP-1 in different degrees.The production of MCP-1 mainly by macrophages sug-gests that they play an important role in the recruit-ment of additional monocytes to the atheroscleroticplaques.

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熊力军,邓仲端,王国平,夏春枝,徐增绶.单核细胞趋化蛋白-1在兔食饵性动脉粥样硬化病变中的表达[J].中国动脉硬化杂志,1998,6(1):1~5.

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  • 收稿日期:1997-10-28
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