發(fā)布時(shí)間：2018-05-31 10:35

  本文選題：2型糖尿病 + 動(dòng)脈粥樣硬化��； 參考：《蘇州大學(xué)》2016年碩士論文

【摘要】：【目的】建立小鼠2型糖尿病(type 2 diabetes mellitus,T2DM)模型、動(dòng)脈粥樣硬化(atherosclerosis,AS)模型以及2型糖尿病合并動(dòng)脈粥樣硬化(T2DM+AS)模型,探討2型糖尿病血管生成素樣蛋白4(Angiogenin-like protein 4,Angptl4)、炎癥因子與動(dòng)脈粥樣硬化的關(guān)系。【方法】將20只ApoE-/-小鼠隨機(jī)分為對(duì)照組、2型糖尿病組(T2DM組)、動(dòng)脈粥樣硬化組(AS組)、2型糖尿病合并動(dòng)脈粥樣硬化組(T2DM+AS組)。普通飼料喂養(yǎng)對(duì)照組,高脂飼料喂養(yǎng)建立AS組,煙酰胺+鏈脲佐菌素+普通飼料建立T2DM組,煙酰胺+鏈脲菌素+高脂飲食建立T2DM+AS組。對(duì)各組ApoE-/-小鼠動(dòng)脈以及胰腺進(jìn)行常規(guī)及病理學(xué)檢測(cè);酶聯(lián)免疫吸附試驗(yàn)(enzyme linked immunosorbent assay,ELISA)、化學(xué)發(fā)光免疫分析法(chemiluminescent immunoassay,CLIA)等方法檢測(cè)血清中Angptl4、血糖、胰島素、胰島素抵抗指數(shù)(Homeostasis model assessment-IR,HOMA-IR)、甘油三酯(Triacylglycerol,TG)、血漿纖溶酶原激活物抑制物1(plasma plasminogen activator inhibitor-1,PAI-1)、低密度脂蛋白(low density lipoprotein cholesterin,LDL-c)和炎性因子腫瘤壞死因子α(Tumor Necrosis Factorα,TNF-α),轉(zhuǎn)化生長(zhǎng)因子β1(Transforming growth factorβ1,TGF-β1)和C反應(yīng)蛋白(C Reactive Protein,CRP)的含量或濃度;免疫熒光方法分析平滑肌肌動(dòng)蛋白(α-smooth muscle actin,α-SMA)在各組小鼠的動(dòng)脈中表達(dá)的變化;逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(reverse transcription-polymerase chain reaction,RT-PCR)和蛋白質(zhì)印跡(Western Blot)方法檢測(cè)Angptl4、α-SMA、血管內(nèi)皮生長(zhǎng)因子、TNF-α、TGF-β1和CRP在各個(gè)模型小鼠中的表達(dá)變化。【結(jié)果】1)血清生化檢測(cè)顯示:模型組(T2DM組、AS組、T2DM+AS組)Angptl4的含量均低于對(duì)照組,T2DM+AS組中含量最低;與對(duì)照組相比,TNF-α和CRP在A(yíng)S組和T2DM+AS組中有顯著升高,TGF-β1則顯著降低,且T2DM+AS組中變化較AS組更加明顯;各模型組中胰島素水平均顯著降低,T2DM組中HOMA-IR升高,T2DM+AS組中HOMA-IR升高更加明顯;TG//PAI-1/LDL-c在各模型組中均有明顯升高,且T2DM+AS組中比T2DM組和AS組變化更加明顯。2)與對(duì)照組相比,T2DM組的動(dòng)脈內(nèi)膜略有狹窄,有斑點(diǎn)出現(xiàn),有堆疊現(xiàn)象;AS組的動(dòng)脈內(nèi)膜同樣也有斑點(diǎn)、內(nèi)膜狹窄和堆疊現(xiàn)象,且中膜有增厚,α-SMA表達(dá)量升高;T2DM+AS組的動(dòng)脈內(nèi)膜出現(xiàn)斑塊,中膜厚度增加較明顯,α-SMA表達(dá)顯著升高。3)胰腺的HE染色表明,與對(duì)照組相比,AS組的胰腺相對(duì)正常,但有炎性細(xì)胞浸潤(rùn);T2DM組的胰腺小結(jié)間隔不明顯,腺泡萎縮形成空泡;T2DM+AS組的胰腺小葉間隔不明顯,腺泡萎縮形成空泡并有炎性細(xì)胞浸潤(rùn)。4)RT-PCR和Western blot結(jié)果均表明,與對(duì)照組相比,Angptl4在A(yíng)S組和T2DM組中表達(dá)明顯降低,且AS組要低于T2DM組,T2DM+AS組中表達(dá)最低。與對(duì)照組相比,T2DM組中TNF-α,TGF-β1和CRP的表達(dá)沒(méi)有明顯變化;AS組中TNF-α和CRP的表達(dá)升高,TGF-β1的表達(dá)則明顯下調(diào),T2DM+AS組中TNF-α和CRP的表達(dá)顯著高于A(yíng)S組,TGF-β1的表達(dá)則顯著低于A(yíng)S組�！窘Y(jié)論】1)Angptl4在2型糖尿病和動(dòng)脈粥樣硬化中的表達(dá)降低,并且與糖代謝和脂代謝異常有關(guān);2)Angptl4可能通過(guò)對(duì)炎癥因子的調(diào)節(jié)延緩2型糖尿病動(dòng)脈粥樣硬化的發(fā)展,從而在2型糖尿病動(dòng)脈粥樣硬化的發(fā)生和發(fā)展中起保護(hù)作用。
[Abstract]:[Objective] to establish the model of type 2 diabetes (type 2 diabetes mellitus, T2DM), the model of atherosclerosis (atherosclerosis, AS) and the model of type 2 diabetes with atherosclerotic (T2DM+AS), and explore the angiopoietin like protein 4 (Angiogenin-like protein 4, Angptl4) of type 2 diabetes, and the relationship between the inflammatory factors and atherosclerosis. [method] 20 ApoE-/- mice were randomly divided into control group, type 2 diabetes group (group T2DM), atherosclerosis group (group AS), type 2 diabetes with atherosclerosis group (group T2DM+AS). Normal diet feeding control group, high fat diet set up AS group, nicotinamide + streptozotocin + ordinary feed set up T2DM group, nicotinamide + streptozotocin T2DM+AS group was established with high fat diet. Routine and pathological examination of the arteries and pancreas of ApoE-/- mice in each group; enzyme linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA), chemiluminescent immunoassay (chemiluminescent immunoassay, CLIA) and other methods for detecting Angptl4, blood sugar, insulin, and insulin resistance index in serum (Homeostasis model assessment-IR, HOMA-IR), triglyceride (Triacylglycerol, TG), plasma plasminogen activator inhibitor 1 (plasma plasminogen activator inhibitor-1, PAI-1), low density lipoprotein (low) and inflammatory factor alpha (alpha), transforming growth factor alpha. The content or concentration of long factor beta 1 (Transforming growth factor beta 1, TGF- beta 1) and C reactive protein (C Reactive Protein, CRP), and the changes in the expression of smooth muscle actin (alpha -smooth muscle actin, alpha) in the arteries of each group of mice by immunofluorescence; Action, RT-PCR) and Western blot (Western Blot) method were used to detect the expression of Angptl4, alpha -SMA, VEGF, TNF- a, TGF- beta 1 and CRP in each model mice. [results] 1) serum biochemical tests showed that the content of the model group (T2DM group, AS group, T2DM+AS group) was lower than that in the control group. Compared with the group, TNF- alpha and CRP were significantly increased in group AS and T2DM+AS, and TGF- beta 1 decreased significantly, and the changes in T2DM+AS group were more obvious than those in the AS group. The levels of insulin in each model group were significantly decreased, HOMA-IR in T2DM group increased and HOMA-IR increased in T2DM+AS group, and TG//PAI-1/LDL-c was significantly increased in each model group. The changes in the +AS group were more obvious than that of the T2DM group and the AS group. Compared with the control group, the intima of the arterial intima in the T2DM group was slightly narrow, there were spots and stacked. The intima of the arterial intima in the AS group also had spots, intima stenosis and stacking phenomenon, and the middle membrane was thickened and the expression of alpha -SMA increased; the intima of the arterial intima appeared in the T2DM+AS group and the thickness of the middle membrane was increased. The HE staining of the pancreas was significantly higher in.3) HE staining of the pancreas showed that the pancreas of the AS group was relatively normal, but there was inflammatory cell infiltration, the pancreatic nodule interval was not obvious in the T2DM group, the alveolus atrophied to form vacuoles, the pancreatic interlobular septum in the T2DM+AS group was not obvious, the vesicles formed vacuoles and the inflammatory infiltration of.4) in the T2DM group, and Wes RT-PCR and Wes. Tern blot results showed that, compared with the control group, the expression of Angptl4 in the AS group and the T2DM group was significantly lower, and the AS group was lower than the T2DM group, and the expression in the T2DM+AS group was the lowest. Compared with the control group, the TNF- a, TGF- beta 1 and the expression of CRP, the expression of TGF- beta and CRP in the T2DM group was not significantly changed. The expression of TNF- alpha and CRP was significantly higher than that in group AS, and the expression of TGF- beta 1 was significantly lower than that in group AS. [Conclusion] 1) the expression of Angptl4 in type 2 diabetes and atherosclerosis is reduced, and it is associated with abnormal glucose metabolism and lipid metabolism; 2) Angptl4 may delay the development of atherosclerosis in type 2 diabetes by regulating the inflammatory factors. It plays a protective role in the occurrence and development of atherosclerosis in type 2 diabetes.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R587.2

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1 郝艷;2型糖尿病Angptl4及炎癥因子水平與動(dòng)脈粥樣硬化的關(guān)系研究[D];蘇州大學(xué);2016年

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本文編號(hào)：1959317