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硝苯地平对ApoE^-/-小鼠RAW264.7巨噬细胞源性胆固醇逆向转运的影响
  • ISSN号:1000-5404
  • 期刊名称:《第三军医大学学报》
  • 时间:0
  • 分类:R362[医药卫生—病理学;医药卫生—基础医学] R446.1[医药卫生—诊断学;医药卫生—临床医学]
  • 作者机构:[1]第三军医大学西南医院心血管内科,重庆市介入心脏病学研究所,重庆400038
  • 相关基金:国家自然科学基金(81100219)
中文摘要:

目的 探讨硝苯地平对ApoE^-/-小鼠RAW264.7巨噬细胞源性胆固醇逆向转运的影响。 方法 8周龄左右ApoE^-/-小鼠16只,用高脂饲料喂养作为模型,按完全随机分组法分为对照组(n=8)和硝苯地平组(n=8)。将[3H]-胆固醇标记的荷脂RAW264.7小鼠巨噬细胞注入小鼠腹腔,24、48 h时取血液标本,酶法检测血浆总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)的浓度。处死后取小鼠肝脏和小肠,实时定量PCR检测肝脏及小肠ABCA1、ABCG1、SR-BⅠ、LXRα基因的mRNA表达,Western blot检测其蛋白表达。同时,收集48 h小鼠粪便,进行闪烁液计数,分别比较2组[3H]的含量。 结果 与对照组相比,经硝苯地平处理组血浆血脂蛋白水平均无明显变化(P〉0.05);血浆24、48 h闪烁值较对照组分别增加37.02%、22.72%(P〈0.05),粪便[3H]闪烁值较对照组增加43.18%(P〈0.05);硝苯地平组ABCA1、ABCG1、SR-BⅠ、LXRα基因的mRNA和蛋白的表达均有明显升高。 结论 硝苯地平通过增加LXRα及其下游基因ABCA1、ABCG1、SR-BⅠ的表达,从而增强ApoE^-/-小鼠巨噬细胞源性胆固醇逆向转运的效果。

英文摘要:

Objective To investigate whether nifedipine increases macrophage reverse cholesterol transport in ApoE^-/- mice and its effect on the expression of related genes. Methods Sixteen eight-week-old male ApoE^-/- mice (fed with high fat and cholesterol) were randomly divided into 2 groups, control group and nifedipine group. RAW264.7 macrophages were loaded with cholesterol by incubation with acetylated-LDL, labeled with [3H]-cholesterol, and then intraperitoneally injected into the mice. The blood samples were collected in 24 and 48 h after injection, the tissues and feces were collected in 48 h, and plasma concentrations of lipids, including TC, TG, LDL and HDL, were measured by biochemistry analyzer. Blood and feces were analyzed for tracer counts using a liquid scintillation counter. Related mRNA and protein levels of several well-characterized proteins involved in reverse cholesterol transportation, including ABCA1, ABCG1, SR-BⅠ and LXRα, were detected by quantitative real-time PCR and Western blotting. Results There was no significant difference in plasma lipid concentrations between the 2 groups(P〉0.05). The amount of [3H]-tracer were 37.02% and 22.72% higher respective in the 24 and 48 h plasma than in control group, and was 43.18% higher in 48 h feces than in control group (P〈0.5). The expression of related genes and proteins was all significantly enhanced in the nifedipine group than in the control group. Conclusion Nifedipine promotes the macrophage reverse cholesterol transportation through the stimulation of LXRα-dependent expression of ABCA1, ABCG1 and SR-BⅠ.

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期刊信息
  • 《第三军医大学学报》
  • 北大核心期刊(2011版)
  • 主管单位:第三军医大学
  • 主办单位:第三军医大学
  • 主编:钱桂生
  • 地址:重庆市沙坪坝区高滩岩30号第三军医大学学报编辑部
  • 邮编:400038
  • 邮箱:aammt@mail.tmmu.com.cn
  • 电话:023- 68752187
  • 国际标准刊号:ISSN:1000-5404
  • 国内统一刊号:ISSN:50-1126/R
  • 邮发代号:78-91
  • 获奖情况:
  • 先后20余次获全国、全军、教育部和省、市优秀科技...,2003年、2005年两度被评为"国家期刊奖百种重点科...
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  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,美国剑桥科学文摘,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:47530