辛伐他汀对2型糖尿病动脉硬化大鼠血浆VEGF、TGF-β1及CTRP3水平的影响研究

发布时间：2018-03-09 20:04

本文选题：糖尿病　切入点：动脉粥样硬化　出处：《石河子大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:观察2型糖尿病性动脉硬化大鼠血浆血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)、转化生长因子β1(Transforming Growth Factor-β1,TGF-β1)、C1q/TNF相关蛋白3(C1q/Tumor Necrosis Factor-related Protein 3,CTRP3)的表达及辛伐他汀对2型糖尿病性动脉硬化病变的干预作用。方法:(1)选取3周龄雄性SD大鼠,体质量为160g~200g,分为正常对照组(NC组,n=8)、高脂饮食组(HFD组,n=8)、高脂干预组(HFD+S组,n=8)、模型组(M组即糖尿病动脉硬化组,n=28)、模型干预组(M+S组即糖尿病动脉硬化干预组,n=16)。(2)采用单次腹腔注射链脲佐菌素溶液45 mg/kg,维生素D3注射液按总剂量50万U/kg分次灌胃,联合高脂饮食饲养的方法建立2型糖尿病合并动脉硬化大鼠模型,以血糖水平和胸主动脉常规组织形态学结果作为评价动物模型成功的标准。(3)HFD+S组和M+S组大鼠给予辛伐他汀溶液20 mg/(kg·d)灌胃进行干预,NC组、HFD组和M组大鼠给予蒸馏水20 m L/(kg·d)灌胃作为对照。(4)采用干化学法测定空腹血糖(fasting plasma glucose,FPG);采用液相平衡竞争放射免疫分析法检测血浆空腹胰岛素(fasting insulin,FINS);采用全自动生物化学分析仪检测血清总胆固醇(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);采用双抗体夹心酶联免疫吸附法检测血浆VEGF、TGF-β1和CTRP3的水平。结果:(1)组织形态学:NC组、HFD+S组动脉光镜下未见病理形态学改变;HFD组动脉可见少量泡沫细胞;M组动脉可见粥样斑块,表层可见纤维帽,其下可见数量不等的泡沫细胞,深层含大量坏死物质、脂质沉积、胆固醇结晶及钙盐沉积,中膜平滑肌纤维增生且排列不规则,弹力纤维断裂;M+S组动脉未见明显粥样斑块,病变较M组明显减轻。(2)与NC组相比,HFD组FINS、HOMA-IR、VEGF、TGF-β1、CTRP3明显增高,M组体质量、FINS明显降低,而FPG、HOMA-IR、TC、TG、LDL、VEGF、TGF-β1明显增高;与HFD组相比,HFD+S组TGF-β1、CTRP3明显增高,M组体质量、FINS、CTRP3明显降低,而FPG、TC、TG、LDL、HDL、VEGF明显增高;与M组相比,M+S组FPG、TC、TG、LDL、HDL、VEGF明显降低,FINS、TGF-β1、CTRP3明显增高(P0.05)。(3)相关分析显示:血浆VEGF与TC、TG、LDL、FPG、HOMA-IR呈正相关,与体质量、FINS呈负相关;TGF-β1与CTRP3、TG呈正相关,与HDL呈负相关;CTRP3与TGF-β1呈正相关,与TC、HDL呈负相关。(4)多元线性逐步回归显示,FPG、TG、HDL、LDL是VEGF水平的影响因素;CTRP3是TGF-β1水平的影响因素;TG、TGF-β1是CTRP3水平的影响因素。结论:(1)VEGF、TGF-β1、CTRP3可能参与糖尿病性动脉硬化的发生,其中,VEGF能促进糖尿病性动脉硬化的发生,TGF-β1和CTRP3对糖尿病性动脉硬化具有保护作用。(2)辛伐他汀能够调脂,改善胰岛功能,降低血糖,下调VEGF、上调TGF-β1、CTRP3的表达,减轻糖尿病大血管病变,在人类是否也有同样的作用还有待进一步研究。
[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- 伪 -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.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.2

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