辛伐他汀對(duì)2型糖尿病動(dòng)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(diǎn):動(dòng)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(dòng)脈硬化大鼠血漿血管內(nèi)皮生長(zhǎng)因子(Vascular Endothelial Growth Factor,VEGF)、轉(zhuǎn)化生長(zhǎng)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(dá)及辛伐他汀對(duì)2型糖尿病性動(dòng)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(duì)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(dòng)脈硬化組,n=28)、模型干預(yù)組(M+S組即糖尿病動(dòng)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(dòng)脈硬化大鼠模型,以血糖水平和胸主動(dòng)脈常規(guī)組織形態(tài)學(xué)結(jié)果作為評(píng)價(jià)動(dòng)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(jìn)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(duì)照。(4)采用干化學(xué)法測(cè)定空腹血糖(fasting plasma glucose,FPG);采用液相平衡競(jìng)爭(zhēng)放射免疫分析法檢測(cè)血漿空腹胰島素(fasting insulin,FINS);采用全自動(dòng)生物化學(xué)分析儀檢測(cè)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(cè)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(dòng)脈光鏡下未見病理形態(tài)學(xué)改變;HFD組動(dòng)脈可見少量泡沫細(xì)胞;M組動(dòng)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(xì)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(dòng)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(fù)相關(guān);TGF-β1與CTRP3、TG呈正相關(guān),與HDL呈負(fù)相關(guān);CTRP3與TGF-β1呈正相關(guān),與TC、HDL呈負(fù)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(dòng)脈硬化的發(fā)生,其中,VEGF能促進(jìn)糖尿病性動(dòng)脈硬化的發(fā)生,TGF-β1和CTRP3對(duì)糖尿病性動(dòng)脈硬化具有保護(hù)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(dá),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(jìn)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(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:R587.2
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