2型糖尿病性动脉粥样硬化大鼠血浆VEGF、TGF-β1、CTRP3的表达及辛伐他汀的干预作用

Serum levels of VEGF, TGF-β1 and CTRP3 in typeⅡdiabetic rat with atherosclerosis and the interventional mechanism of simvastatin

目的观察2型糖尿病性动脉粥样硬化大鼠血浆血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、C1q/TNF相关蛋白3(CTRP3)的表达及辛伐他汀的干预作用。方法将SD大鼠随机分为正常饮食(NC)组(n=8)、高脂饮食(HFD)组(n=8)、高脂干预(HFD+S)组(n=8)、模型(M)组(n=18)、模型干预(M+S)组(n=16)。采用链脲佐菌素+维生素D3+高脂饮食建立糖尿病动脉粥样硬化大鼠模型,HFD+S、M+S组用辛伐他汀溶液20 mg/(kg·d)灌胃进行干预,蒸馏水20 m L/(kg·d)灌胃作为对照。测定各组大鼠空腹血糖(FPG)、血脂、空腹胰岛素(FINS)、VEGF、TGF-β1、CTRP3的水平。结果 M组动脉病理可见明显粥样斑块,M+S组病变较M组明显减轻。HFD组VEGF、TGF-β1及CTRP3高于NC组;M组VEGF、TGF-β1高于NC组,VEGF高于HFD组,CTRP3低于HFD组。辛伐他汀干预后,HFD+S组TGF-β1、CTRP3高于HFD组,M+S组VEGF低于M组,且TGF-β1、CTRP3均高于M组(P<0.05)。结论 VEGF、TGF-β1、CTRP3可能参与糖尿病性动脉粥样硬化的发生,辛伐他汀除降脂外,还能下调VEGF、上调TGF-β1、CTRP3表达,并对糖尿病性动脉粥样硬化发挥保护作用。

Objective To investigate the serum expressions of vascular endothelial growth factor （VEGF）, transforming growth factor-β1 （TGF-β1） and C1q/tumor necrosis factor-related protein 3 （CTRP3） in type II diabetic rats with atheroscle？rosis and to undermine the interventional mechanism of simvastatin. Methods SD rats were randomly divided into normal diet （NC） group （n=8）, high-fat diet （HFD） group （n=8）, high-fat diet intervention （HFD＋S） group （n=8）, model （M） group （n=18） and model intervention （M＋S） group （n=16）. The diabetic atherosclerosis model was established by streptozotocin （STZ）＋Vitamin D3（VitD3）＋High-fat diet. The group HFD＋S and group M＋S rats were administrated with simvastatin at 20 mg/（kg＆#183;d）intragastrically as intervention while distilled water [20 mL/（kg＆#183;d）] were given to other groups. Serum levels of fasting plasma glucose（FPG）, blood lipid, fasting insulin（FINS）, VEGF, TGF-β1 and CTRP3 were compared between each groups. Results Characteristics of atheromatous plaque were seen in group M and group M＋S whose pathological change were markedly attenuated compared to group M. Serum levels of VEGF, TGF-β1 and CTRP3 were significantly high？er in rats from Group HFD than those in rats from group NC. Serum levels of VEGF and TGF-β1 were significantly higher in rats from Group M than those in rats from group NC. Serum level of VEGF was significantly higher in rats from Group M than it in rats from group HFD. Serum level of CTRP3 was significantly lower in rats from Group M than it in rats from group HFD. Moreover, serum levels of TGF-β1 and CTRP3 were significantly higher in rats from Group HFD＋S than those in rats from group HFD after the intervention with simvastatin. Serum level of VEGF was significantly lower in rats from Group M＋S than it in rats from group M, and serum levels of TGF-β1 and CTRP3 were significantly higher in rats from group M＋S than those in rats from group M after the intervention with simvastatin. Conclusion VEGF, TGF-β1 and CTRP3 may partici？pate in development of diabetic atherosclerosis. In addition to its hypolipidemic role, Simvastatin can also down regulate se？rum level of VEGF and up regulate serum levels of TGF-β1 and CTRP3 to exert a significant protective effect on diabetic atherosclerosis.