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山东大学学报(医学版)

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人巨细胞病毒和糖基化终产物共同作用对血管内皮细胞的影响

李树英1, 吴建敏1,周亚滨1,张风雷1,程轶喆1,于晗1,齐眉1,唐伟1,王红1,刘娟1   

  1. 1. 实验畸形学教育部重点实验室山东大学医学院微生物教研室;2. 山东省齐鲁医院心内科, 山东 济南 250012
  • 收稿日期:2007-01-09 修回日期:1900-01-01 出版日期:2007-05-24 发布日期:2007-05-24
  • 通讯作者: 周亚滨

Co-effects of human cytomegalovirus infection and advanced glycation end products on vascular endothelial cells

LI Shu-ying1, WU Jian-min1,ZHOU Ya-bin1,ZHANG Feng-lei1,CHENG Yi-zhe1,YU Han1,QI Mei1,TANG Wei1,王红1,LIU Juan1   

  1. 1.Key Laboratory of Experimental Teratology, Ministry of Education;Department of Microbiology, School of Medicine;2.Department of Cardiology, Shandong University
  • Received:2007-01-09 Revised:1900-01-01 Online:2007-05-24 Published:2007-05-24
  • Contact: ZHOU Ya-bin

摘要: 目的:观察人巨细胞病毒(human cytomegalovirus,HCMV)和糖基化终产物(advanced glycation end products, AGEs)共同作用对血管内皮细胞(vein endothelial cells,ECV)氧化应激的影响及对糖基化终产物受体(the receptor for advanced glycation end products, RAGE)表达的影响,明确HCMV和AGEs在致内皮细胞损伤作用中是否具有协同效应,探讨HCMV和AGEs致动脉粥样硬化 (AS)发生和发展的可能机制。方法:用HCMV和AGEs分别及共同作用于ECV,将实验对象分为:对照组、HCMV组、牛血清白蛋白(BSA)组、AGEs组、AGEs+HCMV组5组;用激光共聚焦显微镜检测细胞内活性氧(ROS)的改变;采用RT-PCR方法检测血管内皮细胞RAGEmRNA的表达。结果:HCMV感染ECV后,对照组荧光强度和BSA组荧光强度均较弱,两组间比较差异无统计学意义(P>0.05);AGEs组和HCMV组荧光强度强于对照组(P<0.01);AGEs+HCMV组荧光强度高于AGEs组和HCMV组(P<0.05),两者联合作用存在协同效应。对照组和BSA组ECV细胞RAGEmRNA均有低水平表达,两组之间比较无差异(P>0.05);AGEs组和HCMV感染组RAGEmRNA表达量高于对照组(P<0.01);AGEs+HCMV组表达量高于AGEs组和HCMV组(P<0.01)。在相同病毒滴度感染的情况下,随AGEs浓度增加RAGEmRNA的表达增高,呈浓度依赖性;在相同AGEs浓度作用时,随HCMV感染滴度增加RAGEmRNA的表达水平升高,呈滴度依赖性。各组之间比较差异有统计学意义(P<0.05)。结论:HCMV和AGEs均能够增强血管内皮细胞氧化应激,促进RAGEmRNA的表达,两者共同作用时呈协同效应。HCMV和AGEs有可能通过协同增强氧化应激、进一步上调RAGEmRNA的表达,介导血管内皮细胞的炎症反应,促进动脉粥样硬化的发生、发展。

关键词: 受体 , 氧化应激, 糖基化终产物, 血管内皮细胞, 人巨细胞病毒

Abstract: Objective: To study the mechanisms of human cytomegalovirus(HCMV) infection in atherosclerosis by investigating changes of reactive oxygen species (ROS) and sequential changes of the receptor of advanced glyca-Methods: Vascular endothelial cells were cultured and then infected with HCMV, then changes of reactive oxygen species were identified by confocal microscopy; Expression of RAGEmRNA was determined by the reverse transcriptase polymerase chain reaction. Results: Fluorescence intensity was determined at a low level in the control group and the BSA group, with no significant difference (P>0.05). However, it was obviously higher in the AGEs group and the HCMV group than in the control group (P<0.01) and it was further increased in the HCMV combined with AGEs group, which was significantly higher than that in the AGEs and the HCMV groups (P<0.01). RAGEmRNA was expressed at a low level in the control group and the BSA group, with no significant difference (P>0.05). However, it was obviously higher in the HCMV group and the AGEs group than in the control group (P<0.01), and was further increased in the HCMV combined with AGEs group, which was significantly higher than that in the AGEs group and the HCMV group (P<0.01). RAGE mRNA expression gradually increased by an increase of AGEs concentration with the same trites of HCMV in a concentration-dependent manner and was also gradually enhanced by an increase of HCMV trite with the same concentration of AGEs in a trite-dependent manner. Conclusions: Both HCMV infection and AGEs can enhance the oxidative stress and the expression of RAGEmRNA in vascular endothelial cells in a co-effects manner. Both HCMV and AGEs have an effect on the injury of vascular endothelial cells by enhancing the oxidative stress and up-regulating the RAGE expression on endothelial cells, which further facilitates the occurrence and development of atherosclerosis.

Key words: Human cytomegalovirus, Advanced glycation end products, Vascular endothelial cells, Reactive oxygen species, Receptor

中图分类号: 

  • R373
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