Urantide对实验性动脉粥样硬化大鼠C反应蛋白表达的影响

Effect of Urantide on the Expression of C-reactive protein in the Experimental Atherosclerosis Rats

目的观察urantide对动脉粥样硬化大鼠C反应蛋白表达的影响,探讨其防治动脉粥样硬化的作用机制。方法采用高脂饲料喂养及腹腔注射维生素D3损伤动脉内膜的方法建立大鼠动脉粥样硬化模型,随机分为四组:对照组、模型组、氟伐他汀组、urantide组,免疫组织化学法检测主动脉壁内C反应蛋白的表达水平。体外培养血管平滑肌细胞,随机分为四组:对照组、尾加压素Ⅱ组、氟伐他汀组、urantide组,酶联免疫吸附法检测各组培养上清中C反应蛋白浓度。结果在胸主动脉内膜及中膜斑块内,模型组C反应蛋白阳性颗粒较对照组表达明显增加,urantide组及氟伐他汀组C反应蛋白的表达减少;urantide各浓度组对血管平滑肌细胞培养上清中C反应蛋白的表达均有下调趋势,其中10-6mol/L urantide下调作用最强(P<0.01)。结论尾加压素Ⅱ在动脉粥样硬化中能促进炎症反应标志因子C反应蛋白的大量表达,而这种促进作用可以被尾加压素Ⅱ受体拮抗剂urantide抑制,该研究为临床应用urantide治疗动脉粥样硬化提供新的视角和实验依据。

Aim To observe the influence of urantide on the expression of C-reactive protein（CRP） in rats with atherosclerosis and investigate its mechanism. Methods Model with atherosclerosis was induced by feeding high fat diet and arterial intimal injury of intraperitoneal injection of vitamin D3,rats were randomly divided into four groups： control group,model group,fluvastatin group and urantide group,and the expression of C-reactive protein in aortic wall were detected by immunological histochemical method.Cultured vascular smooth muscle cells in vitro were randomly divided into four groups： control group,urotensinⅡgroup,fluvastatin group and urantide group,and the expression of C-reactive protein in supernanant were detected by enzyme-linked immunosorbent assay（ELISA）. Results In the plaques of thoracic aorta intima and tunica media,the expression of the positive particles of C-reactive protein in the model group was increasing obviously compared with that in the control group and the C-reactive protein expression in each experiment group of urantide was decreasing by fluvastatin.The C-reactive protein expression in the vascular smooth muscle cells supernatant of each urantide concentration group had downward trend,among which the 10-6 mol/L urantide was decreasing most（P0.01）.Conclusions UrotensinⅡ can facilitate the over-expression of C-reactive protein in atherosclerosis.However,the promotion can be inhibited by urotensinⅡ receptor antagonist urantide.The experiment provides new views and experiment basis for the clinic treatment of atherosclerosis with urantide.