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非对称二甲基精氨酸介导3,4,5,6-四羟基口山酮对内皮细胞间通讯的保护作用(英文)

Asymmetric dimethylarginine damages connexin 43-mediated endothelial gap junction intercellular communication 3,4,5,6-tetrahydroxyxanthone preserves intercellular communication by reduction of the endogenous nitric oxide synthase inhibitor level

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【作者】 贾素洁张毕奎赖永全邓汉武李元建

【Author】 Su-Jie Jia~a,b,Bi-Kui Zhang~a,Yong-Quan Lai,Han-Wu Deng~b,Yuan-Jian Li~b,a Department of Pharmaceutics,The Third XiangYa Hospital of Central South University,Changsha,China b Department of Pharmacology,School of Pharmaceutical Sciences,Central South University,Changsha,China

【机构】 中南大学湘雅三医院药剂科中南大学药学院

【摘要】 胞间通讯(Communication viagap junction,GJIC)是以缝隙连接蛋白构成的相邻细胞间的通道结构,是细胞间最重要的信息交流形式,可调节组织细胞的生长、分化参与调节细胞的多种活动。本研究旨在观察中药单体3,4,5,6-四羟基口山酮对人脐静脉内皮细胞缝隙连接蛋白43(Cx43)表达的影响及其对溶血性磷脂酰胆碱(Lysophosphati dylcholine,LPC)所诱导的内皮细胞间通讯抑制的影响。研究结果发现,LPC能够显著抑制人脐静脉内皮细胞GJIC,同时伴有Cx43的mRNA和蛋白表达下调以及细胞培养液中ADMA的蓄积。中药单体3,4,5,6-四羟基口山酮(3,10μM,24h)可以降低LPC所导致的细胞内超氧阴离子生成增多,减少细胞培养液中ADMA的蓄积,同时伴有Cx43表达下调。结论:本实验结果表明3,4,5,6-四羟基口山酮可以抑制LPC所致的内皮细胞间GJIC的功能抑制,此种作用可能与其上调Cx43的表达有关,这可能是3,4,5,6-四羟基口山酮治疗动脉粥样硬化发展的一个新机制。

【Abstract】 Objective To observe the direct effects of 3, 4, 5, 6-tetrahydroxyxanthone on connexin43 (Cx43) expression in cultured endothelial cells. Methods Cells were treated with lysophosphatidylcholine (LPC, 10 mg/L) for 24 h in the presence or absence of different concentration of 3, 4, 5, 6-tetrahydroxyxanthone (1, 3 or 10 μM). The ROS production, cell viability, ADMA levels and Cx43 expression were detected. Results 3, 4, 5, 6-tetrahydroxyxanthone significantly inhibited the increase in ROS production and ADMA level, increased cell viability and upregulated Cx43 mRNA and protein expression induced by LPC. Conclusion 3, 4, 5, 6-tetrahydroxyxanthone has protective effects in LPC induced atherosclerotic lesions, which is at least partly related to reduction of asymmetric dimethylarginine level and downregulation of Cx43 expression. .

【基金】 supported by the National Natural Science Foundation of China (Grant No 30900621)
  • 【会议录名称】 2010年中国药学大会暨第十届中国药师周论文集
  • 【会议名称】2010年中国药学大会暨第十届中国药师周
  • 【会议时间】2010-11
  • 【会议地点】中国天津
  • 【分类号】R96
  • 【主办单位】中国药学会(Chinese Pharmaceutical Association)、天津市人民政府
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