内皮祖细胞外泌体对2型糖尿病动脉粥样硬化小鼠血管内皮细胞炎症反应和氧化应激的调节作用

发布时间：2018-01-30 11:40

本文关键词： 内皮祖细胞外泌体 2型糖尿病动脉粥样硬化炎症反应氧化应激　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:1.探讨2型糖尿病(type 2 diabetes mellitus,T2DM)动脉粥样硬化(atherosclerosis,AS)的发生是否与血管内皮细胞炎症反应和氧化应激有关。2.探究正常小鼠内皮祖细胞外泌体(endothelial progenitor cells-derived exosomes,EPC-Exos)对2型糖尿病AS小鼠血管内皮的修复作用是否与其对血管内皮细胞炎症反应和氧化应激的调节作用有关。方法:小鼠分为2型糖尿病AS造模组(model,MOD)和对照组(control,CON)。MOD组采用C57背景的自发性2型糖尿病db/db小鼠予以高脂饲料喂养;CON组采用C57小鼠联合基础饲料喂养。喂养14周后,将MOD组小鼠随机分为EPC-Exos干预组(MOD+Exos组)和PBS对照组(MOD+PBS组);CON组小鼠分为EPC-Exos干预组(CON+Exos组)和PBS对照组(CON+PBS组)。1周后处死小鼠,酶联免疫吸附法(enzyme-linked immuno sorbent assay,ELISA)比较各组小鼠血清炎症反应指标C-反应蛋白(C-reactive protein,CRP),白细胞介素-8(interleukin-8,IL-8)及氧化应激指标超氧化物歧化酶(superoxide dismutase,SOD),过氧化氢酶(catalase,CAT)和丙二醛(malondialdehyde,MDA)表达水平的变化,并用ROS荧光探针比较各组小鼠腹主动脉之间超氧阴离子型活性氧族(reactive oxygen species,ROS)含量的变化。结果:1.ELISA法检测小鼠血清炎症因子表达水平:与CON+PBS组小鼠相比,MOD+PBS组小鼠血清CRP表达显著增加,IL-8也稍有增加,但无统计学意义;与MOD+PBS组小鼠相比,MOD+Exos组小鼠血清CRP,IL-8表达均显著下降。2.ELISA法检测小鼠血清氧化应激指标表达水平:与CON+PBS组小鼠相比,MOD+PBS组小鼠血清SOD表达水平显著增加,CAT表达显著降低,MDA稍有增加,但无统计学意义;与MOD+PBS组小鼠相比,MOD+Exos组小鼠血清SOD与MDA均明显降低,CAT稍有降低,但无统计学意义;与CON+Exos组小鼠相比,MOD+Exos组小鼠血清CAT表达显著降低。3.小鼠腹主动脉ROS荧光探针:与CON组小鼠相比,MOD组小鼠腹主动脉超氧阴离子型ROS含量明显增高;与MOD+PBS组小鼠相比,MOD+Exos组小鼠腹主动脉超氧阴离子型ROS含量明显降低。结论:1.2型糖尿病AS与血管内皮细胞炎症反应及氧化应激密切相关。2.EPC-Exos可减少CRP和IL-8的表达,从而抑制2型糖尿病AS小鼠血管内皮细胞的炎症反应。3.EPC-Exos可减少ROS,并抑制MDA的表达,从而抑制2型糖尿病AS小鼠血管内皮细胞的氧化应激。4.EPC-Exos对2型糖尿病AS血管内皮的修复作用可能与其抑制血管内皮细胞的炎症反应和氧化应激,减少对血管的损害有关。
[Abstract]:Objective to investigate atherosclerosis of type 2 diabetes mellitus type 2 diabetes mellitusus T2DMm. Whether the occurrence of ASA is related to inflammation of vascular endothelial cells and oxidative stress. 2. To explore the exocrine of endothelial progenitor cells (EPCs) in normal mice (. Endothelial progenitor cells-derived exosomes. EPC-Exos). Whether the repair of vascular endothelium in type 2 diabetic as mice is related to its role in regulating the inflammatory response of vascular endothelial cells and oxidative stress. Methods: the mice were divided into type 2 diabetes mellitus as model group (. Model. Db/db mice with C57 background spontaneous type 2 diabetes mellitus were fed with high fat diet. The CON group was fed with C57 mice combined with basic diet for 14 weeks. The mice in MOD group were randomly divided into EPC-Exos intervention group (Mod Exos group) and PBS control group (Mod PBS group). The mice in CON group were divided into EPC-Exos intervention group (Con Exos group) and PBS control group (Con PBS group). Enzyme-linked immuno sorbent assay was detected by enzyme-linked immunosorbent assay (Elisa). ELISAA was used to compare the serum inflammatory response index C-reactive protein (CRP) in each group. Interleukin-8 (IL-8) and superoxide dismutase (SOD). Changes of catalase (CAT) and malondialdehyde (malondialdehyde) (MDAs) expression levels. The reactive oxygen species of superoxide anion reactive oxygen species (Ros) between the abdominal aorta of each group was compared with ROS fluorescence probe. Results: 1. Elisa method was used to detect the expression of serum inflammatory factors in mice: compared with CON PBS group. In MOD PBS group, the expression of serum CRP increased slightly, but there was no statistical significance. Compared with the mice of MOD PBS group, the serum CRP of Mod Exos group was higher than that of Mod Exos group. The expression of IL-8 was significantly decreased. 2. The expression of serum oxidative stress index was detected by Elisa: compared with CON PBS group. The level of serum SOD expression in MOD PBS group was significantly increased, but the expression of cat was significantly decreased, but there was no significant difference between the two groups. Compared with the MOD PBS group, the serum SOD and MDA decreased slightly in the Mod Exos group, but there was no significant difference between the two groups. Compared with the CON Exos group, the serum CAT expression in the Mod Exos group was significantly lower than that in the CON Exos group. 3.The ROS fluorescence probe in the abdominal aorta of the mice was compared with that in the CON group. The content of superoxide anion type ROS in abdominal aorta of MOD group was significantly higher than that in control group. Compared with MOD PBS group. The content of superoxide anion type ROS in abdominal aorta of MOD Exos group was significantly decreased. Type 1.2 Diabetic as was associated with vascular endothelial cell inflammation and oxidative stress. 2. EPC-Exos could reduce the expression of CRP and IL-8. EPC-Exos could inhibit the inflammatory response of vascular endothelial cells in type 2 diabetic as mice. 3. EPC-Exos could reduce the expression of ROSand inhibit the expression of MDA. Thus inhibiting oxidative stress of vascular endothelial cells in type 2 diabetic as mice. 4. The repair effect of EPC-Exos on vascular endothelial cells of type 2 diabetes mellitus may be related to its inhibition of inflammatory response of vascular endothelial cells. Oxidative stress. Reduced damage to blood vessels.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2

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