对照组、模型组及免疫组，每组10只，后二组造大鼠动脉粥样硬化模型，免疫组于饲养第5周给予外泌体尾静脉注射。所有大鼠第8周取材，观察外周血中游离血管内皮细胞，分离血清，分别检测各组大鼠血清中生化指标[血糖、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]水平、細胞因子[白介素-2（IL-2）、白介素-4（IL-4）、γ-干扰素（IFN-γ）]的mRNA表达水平，以及炎症因子[肿瘤坏死因子（TNF-α）、白介素-1（IL-1）、内皮素-1（ET-1）、一氧化氮（NO）]表达水平。 结果 成功培养传代血管内皮细胞，大鼠造模成功。模型组大鼠血糖、TG、TC、HDL-C及LDL-C与对照组比较，差异有高度统计学意义（P < 0.01）;免疫组TG、TC与LDL-C低于模型组（P < 0.05或P < 0.01）。与对照组比较，成模后各细胞因子及TNF-α、IL-1、ET-1水平均明显升高，血清NO水平明显降低（P < 0.01）;与模型组比较，免疫组细胞因子及TNF-α、IL-1、ET-1水平均明显降低，血清NO水平明显升高（P < 0.05或P < 0.01）。镜下，模型组外周血内皮细胞数明显增多，而免疫组虽较对照组计数略增，但血管内皮细胞数量少于模型组。结论 在动脉粥样硬化的病理过程中，内皮细胞源性外泌体可能保护受损内皮细胞，缓冲免疫应答，减轻炎症损害，降低临床指标。
[关键词] 动脉粥样硬化;内皮细胞;外泌体;内皮损伤;免疫应答;细胞因子
[中图分类号] R543.5 [文献标识码] A [文章编号] 1673-7210（2019）11（c）-0007-07
Effect of endothelial cell-derived exosomes on immune factors in atherosclerotic rats
LUO Xueting1 ZHOU Yong2 JIANG Manhong2 LUO Baoping1
1.The First Clinical College， Hubei University of Chinese Medicine，Hubei Province， Wuhan 430000， China; 2.Department of Oncology， Affiliated Hospital of Hubei University of Chinese Medicine， Hubei Province， Wuhan 430000， China
[Abstract] Objective To investigation the effect of vascular endothelial cells derived exosomes on the immune response and inflammatory damage mechanism in atherosclerotic rats. Methods Vascular endothelial cells derived exosomes were cultivated and identified. Thirty Wistar rats were divided into three groups according to the random digital table method， including the control， model and immune groups， 10 rats in each group. The latter two groups were used to establish atherosclerotic models， and the immune group was injected with exosomes at the fifth week of feeding. Vascular endothelial cells were separated from rat serum at the eighth week to detect the biochemical criterion [blood glucose， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， mRNA expression of cytokine [interleukin-2 （IL-2）， interleukin-4 （IL-4）， γ-interferon （IFN-γ）] and expression levels of inflammatory factor [tumor necrosis factor （TNF-α）， interleukin-1 （IL-1）， endothelin-1 （ET-1） and nitric oxide （NO）]. Results Vascular endothelial cells and rat model were established successfully. Compared with the control group， the differences of blood glucose， TG， TC， HDL-C， LDL-C in the model group were highly statistically significant （P < 0.01）. The TG， TC and LDL-C of the immune group were lower than those of the model group （P < 0.05 or P < 0.01）. Compared with the control group， the levels of cytokines， TNF-α， IL-1 and ET-1 were significantly increased and the level of serum NO was significantly decreased after the modeling （P < 0.01）. Compared with the model group， the levels of cytokines， TNF-α， IL-1 and ET-1 in the immune group were significantly decreased， and the serum NO level was significantly increased （P < 0.05 or P < 0.01）. The number of peripheral blood endothelial cells in the model group was significantly increased under the microscope. The number of peripheral blood endothelial cells in the immue group had slight increase， but was than that in the model group. Conclusion In the pathological process of atherosclerosis， vascular endothelial cells derived exosomes may protect the damaged endothelial cells， alleviate immune response and inflammatory damage， and reduce the clinical indicators.
推荐访问： 内皮 硬化 动脉 因子 免疫
