肺炎衣原体致血管动脉硬化发生机制的实验研究

发布时间：2018-01-07 02:24

本文关键词：肺炎衣原体致血管动脉硬化发生机制的实验研究　出处：《吉林大学》2006年博士论文　论文类型：学位论文

【摘要】：本实验通过体内外病理模型探讨了肺炎衣原体感染在动脉粥样硬化形成和发展中的作用。体外培养人脐静脉血管内皮细胞,用肺炎衣原体(CWL-029)感染血管内皮细胞,应用RT-PCR的方法检测肺炎衣原体对血管内皮细胞单核细胞趋化蛋白-1(MCP-1)和白介素-8(IL-8)mRNA表达的影响,进一步应用Western Blot检测转录因子(NF-κ Bp65)蛋白的变化,探索NF-κ Bp65在肺炎衣原体致动脉粥样硬化中的作用及其调控机制。同时建立C57BL/6J小鼠肺炎衣原体感染动物模型,并观察了大环内脂类药物(克拉霉素)的治疗效果。结果表明:肺炎衣原体能够感染脐静脉血管内皮细胞,并发现细胞内MCP-1、IL-8 mRNA表达增强,且有时相性变化。IL-8mRNA表达8小时达到高峰,MCP-1 mRNA表达12小时达到高峰。肺炎衣原体感染血管内皮细胞,使其细胞核内NF-κ Bp65蛋白表达增强,在感染后0.5小时开始增加,1小时达峰值,表明转录因子NF-κ Bp65明显的核移位,说明肺炎衣原体激活了血管内皮细胞NF-κ B信号传导通路,通过NF-κ B介导MCP-1、IL-8等炎症介子的过度表达而在动脉粥样硬化的发生发展中起作用。肺炎衣原体感染加重了高脂血症小鼠的IL-6和IL-8水平的升高,表明肺炎衣原体感染协同高脂血症诱导和/或促进动脉粥样硬化的形成。大环内脂类药物通过早期治疗预防或延期治疗能够减轻肺炎衣原体感染所致动脉粥样硬化的形成,肺炎衣原体感染是动脉粥样硬化形成和发展的因素之一。
[Abstract]:In this study, the role of chlamydia pneumoniae infection in the formation and development of atherosclerosis in vitro and in vivo was studied. Human umbilical vein endothelial cells were cultured in vitro. The vascular endothelial cells were infected with chlamydia pneumoniae (CWL-029). The effects of chlamydia pneumoniae on the expression of monocyte chemoattractant protein (MCP-1) and interleukin-8 (IL-8) mRNA in vascular endothelial cells were detected by RT-PCR. Furthermore, Western Blot was used to detect the change of NF- 魏 Bp65) protein. To explore the role of NF- 魏 Bp65 in chlamydia pneumoniae induced atherosclerosis and its regulatory mechanism, and to establish C57BL / 6J mice model of chlamydia pneumoniae infection. The results showed that chlamydia pneumoniae could infect endothelial cells of umbilical vein and found intracellular MCP-1. The expression of IL-8mRNA was enhanced, and sometimes the expression of IL-8 reached its peak at 8 hours after phase change. The expression of MCP-1 mRNA reached its peak at 12 hours. Chlamydia pneumoniae infected vascular endothelial cells (VEC) and increased the expression of NF- 魏 Bp65 protein in the nucleus of chlamydia pneumoniae. The peak value of NF- 魏 Bp65 increased to 1 hour at 0.5 h after infection, indicating that the nuclear translocation of the transcription factor NF- 魏 Bp65 was obvious. These results suggest that chlamydia pneumoniae activates NF- 魏 B signaling pathway in vascular endothelial cells and mediates MCP-1 through NF- 魏 B. The overexpression of inflammatory mesons such as IL-8 plays an important role in the development of atherosclerosis. Chlamydia pneumoniae infection exacerbates the increase of IL-6 and IL-8 levels in hyperlipidemic mice. The results indicate that chlamydia pneumoniae infection combined with hyperlipidemia induces and / or promotes the formation of atherosclerosis. Macrocyclic lipids can reduce atherosclerosis caused by chlamydia pneumoniae infection by early treatment or delayed treatment. The formation of metamorphosis. Chlamydia pneumoniae infection is one of the factors in the formation and development of atherosclerosis.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R374

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