辛伐他汀對2型糖尿病動脈硬化大鼠血漿VEGF、TGF-β1及CTRP3水平的影響研究
本文選題:糖尿病 切入點:動脈粥樣硬化 出處:《石河子大學(xué)》2015年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:觀察2型糖尿病性動脈硬化大鼠血漿血管內(nèi)皮生長因子(Vascular Endothelial Growth Factor,VEGF)、轉(zhuǎn)化生長因子β1(Transforming Growth Factor-β1,TGF-β1)、C1q/TNF相關(guān)蛋白3(C1q/Tumor Necrosis Factor-related Protein 3,CTRP3)的表達及辛伐他汀對2型糖尿病性動脈硬化病變的干預(yù)作用。方法:(1)選取3周齡雄性SD大鼠,體質(zhì)量為160g~200g,分為正常對照組(NC組,n=8)、高脂飲食組(HFD組,n=8)、高脂干預(yù)組(HFD+S組,n=8)、模型組(M組即糖尿病動脈硬化組,n=28)、模型干預(yù)組(M+S組即糖尿病動脈硬化干預(yù)組,n=16)。(2)采用單次腹腔注射鏈脲佐菌素溶液45 mg/kg,維生素D3注射液按總劑量50萬U/kg分次灌胃,聯(lián)合高脂飲食飼養(yǎng)的方法建立2型糖尿病合并動脈硬化大鼠模型,以血糖水平和胸主動脈常規(guī)組織形態(tài)學(xué)結(jié)果作為評價動物模型成功的標(biāo)準(zhǔn)。(3)HFD+S組和M+S組大鼠給予辛伐他汀溶液20 mg/(kg·d)灌胃進行干預(yù),NC組、HFD組和M組大鼠給予蒸餾水20 m L/(kg·d)灌胃作為對照。(4)采用干化學(xué)法測定空腹血糖(fasting plasma glucose,FPG);采用液相平衡競爭放射免疫分析法檢測血漿空腹胰島素(fasting insulin,FINS);采用全自動生物化學(xué)分析儀檢測血清總膽固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL);采用雙抗體夾心酶聯(lián)免疫吸附法檢測血漿VEGF、TGF-β1和CTRP3的水平。結(jié)果:(1)組織形態(tài)學(xué):NC組、HFD+S組動脈光鏡下未見病理形態(tài)學(xué)改變;HFD組動脈可見少量泡沫細胞;M組動脈可見粥樣斑塊,表層可見纖維帽,其下可見數(shù)量不等的泡沫細胞,深層含大量壞死物質(zhì)、脂質(zhì)沉積、膽固醇結(jié)晶及鈣鹽沉積,中膜平滑肌纖維增生且排列不規(guī)則,彈力纖維斷裂;M+S組動脈未見明顯粥樣斑塊,病變較M組明顯減輕。(2)與NC組相比,HFD組FINS、HOMA-IR、VEGF、TGF-β1、CTRP3明顯增高,M組體質(zhì)量、FINS明顯降低,而FPG、HOMA-IR、TC、TG、LDL、VEGF、TGF-β1明顯增高;與HFD組相比,HFD+S組TGF-β1、CTRP3明顯增高,M組體質(zhì)量、FINS、CTRP3明顯降低,而FPG、TC、TG、LDL、HDL、VEGF明顯增高;與M組相比,M+S組FPG、TC、TG、LDL、HDL、VEGF明顯降低,FINS、TGF-β1、CTRP3明顯增高(P0.05)。(3)相關(guān)分析顯示:血漿VEGF與TC、TG、LDL、FPG、HOMA-IR呈正相關(guān),與體質(zhì)量、FINS呈負相關(guān);TGF-β1與CTRP3、TG呈正相關(guān),與HDL呈負相關(guān);CTRP3與TGF-β1呈正相關(guān),與TC、HDL呈負相關(guān)。(4)多元線性逐步回歸顯示,FPG、TG、HDL、LDL是VEGF水平的影響因素;CTRP3是TGF-β1水平的影響因素;TG、TGF-β1是CTRP3水平的影響因素。結(jié)論:(1)VEGF、TGF-β1、CTRP3可能參與糖尿病性動脈硬化的發(fā)生,其中,VEGF能促進糖尿病性動脈硬化的發(fā)生,TGF-β1和CTRP3對糖尿病性動脈硬化具有保護作用。(2)辛伐他汀能夠調(diào)脂,改善胰島功能,降低血糖,下調(diào)VEGF、上調(diào)TGF-β1、CTRP3的表達,減輕糖尿病大血管病變,在人類是否也有同樣的作用還有待進一步研究。
[Abstract]:Objective: to observe the expression of plasma vascular Endothelial Growth factor- 尾 1 transforming Growth factor- 尾 1 TGF- 尾 1 TGF- 尾 1 protein 3C1Q / TNF- 偽 -associated protein 3C1Q / Tumor Necrosis Factor-related Protein 3CTRP3 in rats with type 2 diabetic arteriosclerosis and the effect of simvastatin on type 2 diabetic arteriopathy. Methods male Sprague-Dawley rats aged 3 weeks were selected. The body weight is 160 g / 200g, which is divided into normal control group (NC group), high fat diet group (HFD group), high fat diet group (HFD group), high fat intervention group (HFD S group), model group (group M), diabetic arteriosclerosis group (group 28), model intervention group (group M), diabetic arteriosclerosis intervention group (group 2). Intraperitoneal injection of streptozotocin (45 mg / kg) and vitamin D3 (500,000 U / kg) were administered intragastrically at a total dose of 500,000 U / kg. A rat model of type 2 diabetes mellitus with arteriosclerosis was established by combining with high fat diet. Blood glucose level and conventional histomorphology of thoracic aorta were used as the standard for evaluating the success of animal model. Rats in group M and group M were given simvastatin solution for 20 mg/(kg 路d.) the rats in NC group and M group were treated with distillation. Water 20 mL / kg 路d) was used as control.) fasting plasma glucose was determined by dry chemical method, plasma fasting insulin was detected by liquid equilibrium competitive radioimmunoassay and serum total bile duct was detected by automatic biochemistry analyzer. Total cholesterol cholesterol, triglyceride triglyceride, low density lipoprotein, high density lipoprotein, high density lipoprotein were detected by double antibody sandwich enzyme-linked immunosorbent assay. Results the vascular endothelial growth factor (TGF- 尾 1) and CTRP3 in plasma were detected by double antibody sandwich enzyme-linked immunosorbent assay (TGF- 尾 1). No pathomorphological changes were found in the arteries of HFD group. A fibrous cap is seen on the surface, under which a variety of foam cells are seen, deep with a large number of necrotic substances, lipid deposits, cholesterol crystals and calcium deposits, and smooth muscle fibers proliferating and irregularly arranged in the middle membrane. Compared with NC group, FINSHOMA-IRN VEGFGF-TGF- 尾 1CTRP3 in HFD group was significantly higher than that in NC group, but the body weight of FINSHOMA-IRV TGF- 尾 1-CTRP3 in M group was significantly lower, while FPGHOMA-IRTTCU TGCL TGF- 尾 1 was significantly higher than that in NC group. Compared with the HFD group, the TGF- 尾 1 CTRP3 was significantly increased and the FINSN CTRP3 was significantly decreased in the HFD group, while the level of VEGF in the plasma was significantly higher than that in the M group, and there was a positive correlation between the plasma TGF- 尾 1 CTRP3 level and the TCG-TGG LDGGHOMA-IR in the M group, and the decrease of the TGF- 尾 1 CTRP3 level in the TGF- 尾 1 CTRP3 group was significantly lower than that in the M group, and the correlation analysis showed that the plasma VEGF level was positively correlated with the TGG LDGHOMA-IR of the two groups, and the correlation analysis showed that the plasma TGF- 尾 1 TGF- 尾 1 CTRP3 level was significantly higher in the HFD group than that in the control group (P 0.05. 3). There was a positive correlation between TGF- 尾 1 and CTRP3TG, and a positive correlation between CTRP3 and TGF- 尾 1 with HDL. Multivariate linear stepwise regression analysis showed that TGF- 尾 1 was a factor influencing VEGF level. Conclusion TGF- 尾 1 CTRP3 may be involved in the pathogenesis of diabetic arteriosclerosis. [conclusion] TGF- 尾 1 CTRP3 may be involved in the pathogenesis of diabetic arteriosclerosis. [conclusion] TGF- 尾 1 CTRP3 may be involved in the pathogenesis of diabetic arteriosclerosis, and TGF- 尾 1 CTRP3 may be involved in the pathogenesis of diabetic arteriosclerosis, and TGF- 尾 1 CTRP3 may be involved in the pathogenesis of diabetic arteriosclerosis. TGF- 尾 1 and CTRP3 have protective effect on diabetic arteriosclerosis. Simvastatin can regulate lipid, improve islet function, decrease blood glucose, down-regulate VEGFand up-regulate the expression of TGF- 尾 _ 1CTRP3. Whether the reduction of diabetic macroangiopathy has the same effect in humans remains to be further studied.
【學(xué)位授予單位】:石河子大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號】:R587.2
【參考文獻】
相關(guān)期刊論文 前8條
1 徐文平;;不同濃度STZ腹腔注射與2型糖尿病大鼠模型建立[J];中國民康醫(yī)學(xué);2013年09期
2 彭忠興;甄毅鋒;陳瑞芳;洪銘范;楊焰;劉愛群;蔡小燕;;轉(zhuǎn)化生長因子-β1和斑塊穩(wěn)定性與動脈粥樣硬化性腦梗死關(guān)系的研究[J];實用醫(yī)學(xué)雜志;2011年22期
3 王文東;齊若梅;;轉(zhuǎn)化生長因子β/Smad3信號通路與動脈粥樣硬化[J];中國動脈硬化雜志;2011年10期
4 馬躍東;李德華;;VEGF在心血管疾病治療中作用的研究進展[J];中國老年學(xué)雜志;2011年09期
5 朱斌;柳茵;劉維軍;李琳;;轉(zhuǎn)化生長因子-β1在心血管病中的研究進展[J];中國循證心血管醫(yī)學(xué)雜志;2011年01期
6 趙娟;李相軍;孫波;高海成;任立群;;維生素D_3聯(lián)合高脂飼料建立大鼠動脈粥樣硬化模型[J];實用醫(yī)學(xué)雜志;2009年21期
7 張美玲;王茁伉;彭成;;動脈粥樣硬化動物模型研究進展[J];四川動物;2009年05期
8 李翠玲;轉(zhuǎn)化生長因子β分子生物學(xué)研究進展[J];國外醫(yī)學(xué).免疫學(xué)分冊;1995年03期
相關(guān)博士學(xué)位論文 前1條
1 孫陽;新脂肪因子CTRP3促進新生血管形成及機制研究[D];第四軍醫(yī)大學(xué);2012年
相關(guān)碩士學(xué)位論文 前2條
1 靳瑾;阻斷CD40-CD40L信號途徑對糖尿病大鼠大血管病變的干預(yù)研究[D];石河子大學(xué);2009年
2 姚孟英;血清轉(zhuǎn)化生長因子β_1水平和冠心病臨床關(guān)系研究[D];鄭州大學(xué);2006年
,本文編號:1590043
本文鏈接:http://sikaile.net/yixuelunwen/nfm/1590043.html