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富含胆固醇的脂蛋白对兔主动脉平滑肌细胞脂类堆积的影响及机制

The Effects of Cholesterol-Rich Lipoproteins on Lipid Accumulation in Rabbit Aortic Smooth Muscle Cells and its Mechanism

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【作者】 从容冯友梅宗义强王淳本瞿智玲邓耀祖

【Author】 CONG Rong, FENG You-Mei, ZONG Yi-Qiang, WANG Chun-Ben, QU Zhi-Ling and DENG Yao-Zu (Department of Biochemistry, Tongji Medical University, Wuhan 430030, China)

【机构】 同济医科大学生物化学教研室!武汉430030

【摘要】 为了观察富含胆固醇的脂蛋白对兔主动脉平滑肌细胞脂类堆积的影响及机制,用富含胆固醇的脂蛋白(β- 极低密度脂蛋白、正常低密度脂蛋白和氧化型低密度脂蛋白) 与兔主动脉平滑肌细胞温育48 h 后,发现β- 极低密度脂蛋白、正常低密度脂蛋白和氧化型低密度脂蛋白都能促进平滑肌细胞内总胆固醇和甘油三酯堆积,以β- 极低密度脂蛋白的作用更显著。乳铁蛋白作为低密度脂蛋白受体相关蛋白的一种特异配体,当它与上述脂蛋白共同与平滑肌细胞温育后,发现乳铁蛋白对脂蛋白所致的平滑肌细胞内脂质堆积有抑制作用。乳铁蛋白与标记的β- 极低密度脂蛋白、正常低密度脂蛋白和氧化型低密度脂蛋白的竞争结合实验也进一步发现乳铁蛋白可明显竞争β- 极低密度脂蛋白、正常低密度脂蛋白、氧化型低密度脂蛋白与平滑肌细胞的结合,且对β- 极低密度脂蛋白的竞争抑制作用尤为明显。提示β- 极低密度脂蛋白、正常低密度脂蛋白和氧化型低密度脂蛋白可能主要通过低密度脂蛋白受体相关蛋白介导进入平滑肌细胞,导致平滑肌细胞内脂质堆积。

【Abstract】 Aim To observe the effects of cholesterol-rich lipoproteins [β-very low density lipoprotein (β-VLDL), normal low density lipoprotein (n-LDL)and oxidized low density lipoprotein(ox-LDL)] on lipid accumulation in smooth muscle cells (SMCs) and to explore its mechanism . Methods β-VLDL, n-LDL or ox-LDL was incubated with rabbit aortic SMCs for 48 hours, total cholesterol(TC)and triglyceride(TG)of the cells were extracted and determined. The increasing concentrations of lactoferrin (specific ligand of LDL receptor-related protein ,LRP) were added withβ-VLDL, n-LDL or ox-LDL, respectively, in the culture and TC and TG of the SMCs were determined as above. SMCs were incubated at 4℃ in M199 containing different concentrations of unlabeled lactoferrin and FITC-β-VLDL, FITC-n-LDL or FITC-ox-LDL, respectively, for 4 hours. The cell surface bound lipoproteins were determined by fluorospectrometry. Results β-VLDL, n-LDL and ox-LDL can all increase TC and TG accumulation in SMCs. More TC and TG were accumulated withβ-VLDL as compared with n-LDL or ox-LDL. The effects can be inhibited by lactoferrin. Moreover, lactoferrin competed with FITC-β-VLDL, FITC-n-LDL or FITC-ox-LDL on binding to SMCs. Conclusion β-VLDL, n-LDL and ox-LDL may contribute to lipid accumulation in SMCs by LRP mediated pathway.

【基金】 国家自然科学基金!(39670163)
  • 【文献出处】 中国动脉硬化杂志 ,CHINESE JOURNAL OF ARTERIOSC LEROSIS , 编辑部邮箱 ,1999年04期
  • 【分类号】R362
  • 【被引频次】2
  • 【下载频次】41
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