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

山东大学学报(医学版)

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. 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.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/Abstract

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

李树英,吴建敏,周亚滨,张风雷,程轶喆,于晗,齐眉,唐伟,王红,刘娟 . 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[J]. 山东大学学报(医学版), 2007, 45(5): 441-445.

LI Shu-ying,WU Jian-min,ZHOU Ya-bin,ZHANG Feng-lei,CHENG Yi-zhe,YU Han,QI Mei,TANG Wei,王红,LIU Juan. Co-effects of human cytomegalovirus infection and advanced glycation end products on vascular endothelial cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(5): 441-445.

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