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普伐他汀对泡沫细胞内胆固醇酯的影响及与小凹蛋白-1的关系
  • ISSN号:0371-0874
  • 期刊名称:《生理学报》
  • 时间:0
  • 分类:R332[医药卫生—人体生理学;医药卫生—基础医学] R329.24[医药卫生—人体解剖和组织胚胎学;医药卫生—基础医学]
  • 作者机构:[1]南华大学药物药理研究所,衡阳421001, [2]中南大学药学院药理教研室,长沙410078, [3]南华大学心血管病学研究所,衡阳421001
  • 相关基金:This work was supported by the National Natural Science Foundation of China (No. 30470719).
中文摘要:

本文旨在观察普伐他汀对鼠源巨噬细胞性泡沫细胞内胆固醇酯含量的影响,探讨此作用与小凹蛋白一l的关系。采用体外培养的鼠源性巨噬细胞株作为研究对象,加入氧化低密度脂蛋白(oxidized low density lipoprotein,OX-LDL)使其形成泡沫细胞,运用高效液相色谱测定细胞内胆固醇酯的改变,同时运用Western blot检测细胞中小凹蛋白-1的表达,并观察普伐他汀对细胞内胆固醇酯和小凹蛋白-1影响的量效和时效关系。结果显示:普伐他汀可明显降低泡沫细胞内的胆固醇酯与总胆固醇的比值,且在一定范围内呈剂量依赖性和时间依赖性。在泡沫细胞中加入普伐他汀后能够促进小凹蛋白-1的表达,呈剂量依赖性和时间依赖性。上述结果提示普伐他汀通过降低细胞内胆固醇酯的含量,减轻细胞泡沫化程度。普伐他汀的这一作用可能与促进小凹蛋白-1表达上调有关。

英文摘要:

The purpose of the present study was to investigate the effect of pravastatin on cholesteryl esters in foam cells of murine macrophages and the relation with caveolin-1. RAW 264.7 murine macrophages were coincubated with 80 mg/L oxidized low density lipoprotein (ox-LDL) and pravastatin (0~100μmol FL) respectively for 24 h. When the best control concentration of pravastatin was confirmed, RAW 264.7 murine macrophages were coincubated with 80 mg/L ox-LDL and pravastatin of the best concentration respectively for 0, 6, 12, 24 h. Oil red O dyeing experiment was used to show the lipid droplets in foam cells. High performance liquid chromatography (HPLC) analysis was performed to determine the content of cellular cholesterol. The level of caveolin-1 was determined by Western blot analysis. The result showed that when macrophages were incubated with 80 mg/L ox-LDL, the ratio of cellular cholesteryl ester to total cholesterol (CE/TC) was beyond 50% through HPLC analysis, and a great deal of lipid droplets displayed in cells through Oil red O dyeing experiment, which manifested the formation of the foam cells. Pravastatin could decrease CE in foam cells in a concentration-dependent manner (1~100μmol/L). At the concentration of 100 pmol/L, pravastatin decreased cellular CE more than 50%. The effects of pravastatin on the decrease of CE in murine macrophages also displayed a time-dependent manner (incubated with 100μmol/L pravastatin from 6 to 24 h). Moreover, the expression of caveolin-1 was decreased when the macrophages were incubated with ox-LDL (80 mg/L), while treatment with pravastatin increased the level of caveolin-1 and displayed a concentration-and timedependent manner. These results suggest that pravastatin could inhibit the development of foam cells through the decrease of cellular CE, which may be related to the upregulation of caveolin-1.

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期刊信息
  • 《生理学报》
  • 中国科技核心期刊
  • 主管单位:中国科学院
  • 主办单位:中国生理学会 中国科学院上海生理研究所
  • 主编:王建军
  • 地址:上海岳阳路319号31B楼
  • 邮编:200031
  • 邮箱:actaps@sibs.ac.cn
  • 电话:021-54922832
  • 国际标准刊号:ISSN:0371-0874
  • 国内统一刊号:ISSN:31-1352/Q
  • 邮发代号:4-157
  • 获奖情况:
  • 中国自然科学核心期刊,中国科学院优秀期刊特别奖,荣获首届国家期刊奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,美国生物医学检索系统,美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:8098