高糖致内皮细胞粘附分子基因的过度表达以及槟榔碱的调节作用

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (1): 27-32.

高糖致内皮细胞粘附分子基因的过度表达以及槟榔碱的调节作用

段智变, 汪海

军事医学科学院毒物药物研究所, 北京 100850

收稿日期:2005-10-11 修回日期:2005-11-17 出版日期:2006-01-06 发布日期:2020-10-23
通讯作者: 汪海, 通讯作者, 男, 博士, 研究员, 博士生导师, 研究方向:心血管分子药理和心脑血管创新药研究。 Tel:010-66932651 E-mail:wh@nic .bmi.ac.cn E-mail:wh@nic .bmi.ac.cn
作者简介:段智变, 女, 博士, 研究方向:心血管药理。 Tel:010-66931557 E-mail:duanzhibian6992@yahoo.com .cn 汪海, 通讯作者, 男, 博士, 研究员, 博士生导师, 研究方向:心血管分子药理和心脑血管创新药研究。 Tel:010-66932651 E-mail:wh@nic .bmi.ac.cn
基金资助:
国家重点基础研究发展规划项目( №GT1998051112)

Regulation effect of arecoline on excess expression of adhesive molecules in endothelial cells injuried with high concentration of D-glucose

DUAN Zhi-bian, WANG Hai

Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850 , China

Received:2005-10-11 Revised:2005-11-17 Online:2006-01-06 Published:2020-10-23

摘要/Abstract

摘要： 目的 :观察 D-葡萄糖( D-glucose) 对培养的牛主动脉内皮细胞单核细胞趋化蛋白-1( monocyte che- moattractant protein-1, MCP-1) 、细胞间粘附分子-1( in- tercellular adhesive molecule-1, ICAM-1) 、血管细胞粘附分子-1( vascular cell adhesive molecule1-1, VCAM-1) mRNA 表达水平的影响, 并观察槟榔碱、PPVP、DMH- PPP、辛伐他汀的干预作用, 探讨它们在糖尿病血管并发症中的作用机制。方法 :通过逆转录-聚合酶链式反应技术, 以 β₂-微球蛋白为内参照检测内皮细胞与不同浓度D-葡萄糖作用不同时间后, 以及用槟榔碱、PPVP 、DMHPPP、辛伐他汀预孵育 20 h 后再给予 D-葡萄糖时内皮细胞 MCP-1 、ICAM-1 、VCAM-1mRNA 表达水平的变化。 结果:浓度为 10 、25 和 50 mmol·L^-1的 D-葡萄糖孵育牛主动脉内皮细胞 16 h, 以及浓度为 25 mmol·L^-1 的 D-葡萄糖分别孵育 8 、 16 、24 h 均可使MCP-1 、ICAM-1 及 VCAM-1 mRNA 表达显著上调, 且上调作用有浓度与时间依赖性。 10^-5mmol·L ^-1槟榔碱、PPVP 、DMHPPP 和辛伐他汀与牛主动脉内皮细胞孵育 20 h, 再给予终浓度为 25 mmol·L^-1 的 D-葡萄糖孵育 16 h 后, 与模型组相比, 槟榔碱可显著抑制由 D-葡萄糖诱导的牛主动脉内皮细胞三个炎性基因MCP-1 、ICAM-1 、VCAM-1 mRNA 表达上调 ;PPVP 可显著抑制MCP-1 和ICAM-1 mRNA 表达上调 ;DMHPPP 和辛伐他汀可显著抑制 MCP-1 mRNA 表达上调。结论 :高浓度 D-葡萄糖可诱导牛主动脉内皮细胞 MCP-1, ICAM-1 和 VCAM-1 mRNA 表达水平增加, 槟榔碱、PPVP 、DMHPPP 和辛伐他汀对过量表达的三种炎性因子的抑制作用不同。

关键词: D-葡萄糖, 动脉粥样硬化, 内皮细胞 , 细胞粘附分子, 槟榔碱

Abstract: AIM:To investigate the effects of D-glu- cose on monocyte chemoattractant protein-1 ( MCP-1) , intercellular cell adhesive molecule type-1 ( ICAM-1) , vascular cell adhesive molecule1-1 ( VCAM-1) mRNA ex- pression and the protective effects of arecoline, PPVP, DMHPPP and simvastatin in cultured bovine aorta endo- thelial cells, thereby to explore possible mechanisms by which the compounds prevent the formation of diabetic vascular complications .METHODS:Bovine aorta endo- thelial cells were cultured in vitro with indicated concen- tration of D-glucose for indicated time .After the cells were harvested at the specified situation, the MCP-1, ICAM-1 and VCAM-1 mRNA expression was detected by reverse transcription-polymerase chain reaction( RT-PCR) and normalized to the mRNA level of β-microglobulin in the absence or in the presence of D-glucose or land arec- oline, PPVP, DMHPPP and simvastatin, respectively . RESULTS:The expression of MCP-1, ICAM-1 and VCAM-1 mRNA all increased dose- and time-dependently after treatments with 10, 25, 50 mmol·L ^-1 D-glucose for 16 h and 25 mmol·L^-1 D-glucose for 8, 16, 24 h, re- spectively .Compare with control group, after the bovine aorta endothelial cells were incubated with 10 - 5 mmol·L ^-1arecoline, PPVP, DMHPPP, simvastatin for 20h in advance, respectively, the injury effects which were subsequently induced by 25 mmol·L ^-1 D-glucose for 16h could be prevented .CONCLUSION:Cultured bovine aorta endothelial cells can express MCP-1, ICAM- 1, and VCAM-1 mRNA at a low level, and high concen- tration of D-glucose can induce excess expression .The regulation effects of arecoline, PPVP, DMHPPP and sim- vastatin on the excess expressions are different, respec- tively .

Key words: D-glucose, atherosclerosis , endothelial cells , Cell adhesive molecules , Arecoline

中图分类号:

R965

段智变, 汪海. 高糖致内皮细胞粘附分子基因的过度表达以及槟榔碱的调节作用[J]. 中国临床药理学与治疗学, 2006, 11(1): 27-32.

DUAN Zhi-bian, WANG Hai. Regulation effect of arecoline on excess expression of adhesive molecules in endothelial cells injuried with high concentration of D-glucose[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(1): 27-32.

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