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肝X受体介导肾小球系膜细胞胆固醇外流
  • ISSN号:1671-167X
  • 期刊名称:北京大学学报(医学版)
  • 时间:0
  • 页码:833-836
  • 语言:中文
  • 分类:R334.1[医药卫生—人体生理学;医药卫生—基础医学]
  • 作者机构:[1]南京医科大学附属江苏省人民医院肾脏内科,南京210029, [2]北京大学基础医学院生理及病生理学系 北京大学糖尿病中心 教育部分子心血管重点实验室
  • 相关基金:国家自然科学基金项目(30530340)、教育部科学技术研究重点项目(104001)及教育部教育振兴行动计划特殊专项(“九八五”工程)(985-2-001-111/2)资助.Supported by National Natural Science Foundation of China (30530340), the Key Project of Chinese Ministry of Education ( 104001 ), and Special Fund for Promation of Education, Ministry of Education P. R. C(985-2-001-111/2).
  • 相关项目:代谢性核受体PPARγ在代谢综合征高血压发病中的作用
中文摘要:

目的:探讨肝X受体在肾系膜细胞脂质代谢中的作用及机制。方法:肝X受体两种亚型的表达运用反转录一多聚酶链式反应和蛋白印迹实验方法证实。ATP结合盒蛋白(ATP-binding cassette,ABC)A1和G1的表达水平用实时荧光定量多聚酶链式反应及转染荧光素酶报告基因方法研究。胆固醇的外流量用[^3H]标记胆固醇方法测量。结幂:肝X受体两种亚型在肾、肾小球、系膜细胞中均有表达。肝X受体人工合成配体TO901317处理系膜细胞后,不仅ABCA1表达上调,而且ABCG1的表达也增高,并导致游离胆固醇外流增加。结论:在小鼠肾系膜细胞中存在肝X受体两种亚型的表达,肝X受体能够通过上调ABCA1和ABCG1的表达,增加系膜细胞中游离胆固醇的外流,减轻脂质负荷和细胞损伤。

英文摘要:

Objective: To examine the role of liver X receptors (LXRs) in lipid metabolism in cultured mouse mesangial cells. Methods: To determine whether LXRα and LXRβ are expressed in the kidney, RT-PCR and western blot assay were utilized. Cultured mesangial cells were treated with either vehicle or LXR agonist TO901317(10μmol/L) for 24 hours. Real-time PCR analysis was used to detect ABCA1 and ABCG1 expressions. Cells were also transfected with a human ABCA1 promoter driven luciferase reporter plasmid and then stimulated with or without TO901317 for 24 hours. In order to determine the effect of TO901317 on protein expression of ABCA1, LXRα adenovirus was used to overexpress LXRα in the cultured cells. Finally, [^3H ] cholesterol eftlux assay was performed to evaluate the eftlux of cholesterol upon TO901317 stimulation. Results: Both LXRct and LXRβ were expressed in the kidney, freshly isolated glomeruli and mesangial cells. After treatment with TO901317, both ABCA1 and ABCG1 expressions were induced. Moreover, ABCA1 protein level was increased after the cells were simultaneously treated with LXRα-adenovirus and TO901317. The cholesterol eftlux was also significantly enhanced after TO901317 treatment. Conclusion: LXRα and LXRβ were functionally expressed in mouse mesangial cells. Activation of LXRs enhanced cholesterol efflux possibly through upregulating ABCA1 and ABCG1 expressions in mesangial cells. Therefore, LXR agonist might ameliorate lipid accumulation and reduce related cell injury in mesangial cells.

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期刊信息
  • 《北京大学学报:医学版》
  • 北大核心期刊(2011版)
  • 主管单位:中华人民共和国教育部
  • 主办单位:北京大学
  • 主编:韩启德
  • 地址:北京海淀区学院路38号
  • 邮编:100191
  • 邮箱:
  • 电话:010-82801551
  • 国际标准刊号:ISSN:1671-167X
  • 国内统一刊号:ISSN:11-4691/R
  • 邮发代号:2-489
  • 获奖情况:
  • 1992年全国优秀科技期刊评比三等奖,1996年第二届全国优秀科技期刊评比二等奖,2001年入选中国期刊方阵,被评为“双百”期刊,2007年获得第六届百种中国杰出学术期刊奖
  • 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,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)
  • 被引量:16532