本文關(guān)鍵詞： 內(nèi)皮祖細(xì)胞外泌體 2型糖尿病 動(dòng)脈粥樣硬化 炎癥反應(yīng) 氧化應(yīng)激　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:1.探討2型糖尿病(type 2 diabetes mellitus,T2DM)動(dòng)脈粥樣硬化(atherosclerosis,AS)的發(fā)生是否與血管內(nèi)皮細(xì)胞炎癥反應(yīng)和氧化應(yīng)激有關(guān)。2.探究正常小鼠內(nèi)皮祖細(xì)胞外泌體(endothelial progenitor cells-derived exosomes,EPC-Exos)對(duì)2型糖尿病AS小鼠血管內(nèi)皮的修復(fù)作用是否與其對(duì)血管內(nèi)皮細(xì)胞炎癥反應(yīng)和氧化應(yīng)激的調(diào)節(jié)作用有關(guān)。方法:小鼠分為2型糖尿病AS造模組(model,MOD)和對(duì)照組(control,CON)。MOD組采用C57背景的自發(fā)性2型糖尿病db/db小鼠予以高脂飼料喂養(yǎng);CON組采用C57小鼠聯(lián)合基礎(chǔ)飼料喂養(yǎng)。喂養(yǎng)14周后,將MOD組小鼠隨機(jī)分為EPC-Exos干預(yù)組(MOD+Exos組)和PBS對(duì)照組(MOD+PBS組);CON組小鼠分為EPC-Exos干預(yù)組(CON+Exos組)和PBS對(duì)照組(CON+PBS組)。1周后處死小鼠,酶聯(lián)免疫吸附法(enzyme-linked immuno sorbent assay,ELISA)比較各組小鼠血清炎癥反應(yīng)指標(biāo)C-反應(yīng)蛋白(C-reactive protein,CRP),白細(xì)胞介素-8(interleukin-8,IL-8)及氧化應(yīng)激指標(biāo)超氧化物歧化酶(superoxide dismutase,SOD),過(guò)氧化氫酶(catalase,CAT)和丙二醛(malondialdehyde,MDA)表達(dá)水平的變化,并用ROS熒光探針比較各組小鼠腹主動(dòng)脈之間超氧陰離子型活性氧族(reactive oxygen species,ROS)含量的變化。結(jié)果:1.ELISA法檢測(cè)小鼠血清炎癥因子表達(dá)水平:與CON+PBS組小鼠相比,MOD+PBS組小鼠血清CRP表達(dá)顯著增加,IL-8也稍有增加,但無(wú)統(tǒng)計(jì)學(xué)意義;與MOD+PBS組小鼠相比,MOD+Exos組小鼠血清CRP,IL-8表達(dá)均顯著下降。2.ELISA法檢測(cè)小鼠血清氧化應(yīng)激指標(biāo)表達(dá)水平:與CON+PBS組小鼠相比,MOD+PBS組小鼠血清SOD表達(dá)水平顯著增加,CAT表達(dá)顯著降低,MDA稍有增加,但無(wú)統(tǒng)計(jì)學(xué)意義;與MOD+PBS組小鼠相比,MOD+Exos組小鼠血清SOD與MDA均明顯降低,CAT稍有降低,但無(wú)統(tǒng)計(jì)學(xué)意義;與CON+Exos組小鼠相比,MOD+Exos組小鼠血清CAT表達(dá)顯著降低。3.小鼠腹主動(dòng)脈ROS熒光探針:與CON組小鼠相比,MOD組小鼠腹主動(dòng)脈超氧陰離子型ROS含量明顯增高;與MOD+PBS組小鼠相比,MOD+Exos組小鼠腹主動(dòng)脈超氧陰離子型ROS含量明顯降低。結(jié)論:1.2型糖尿病AS與血管內(nèi)皮細(xì)胞炎癥反應(yīng)及氧化應(yīng)激密切相關(guān)。2.EPC-Exos可減少CRP和IL-8的表達(dá),從而抑制2型糖尿病AS小鼠血管內(nèi)皮細(xì)胞的炎癥反應(yīng)。3.EPC-Exos可減少ROS,并抑制MDA的表達(dá),從而抑制2型糖尿病AS小鼠血管內(nèi)皮細(xì)胞的氧化應(yīng)激。4.EPC-Exos對(duì)2型糖尿病AS血管內(nèi)皮的修復(fù)作用可能與其抑制血管內(nèi)皮細(xì)胞的炎癥反應(yīng)和氧化應(yīng)激,減少對(duì)血管的損害有關(guān)。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2

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