目的:观察urantide对动脉粥样硬化(AS)大鼠胸主动脉损伤的影响,探讨其防治AS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AS模型,随机分为正常组、AS模型组、阳性药组及urantide组。全自动生化分析仪检测大鼠血清中的甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和Ca2+的水平;胸主动脉HE染色观察各组大鼠胸主动脉形态学变化。RT-PCR方法检测大鼠胸主动脉中尾加压素Ⅱ(UⅡ)及其受体G蛋白偶联受体14(GPR14)mRNA的表达。结果:与正常组比较,AS模型组大鼠血清中Ca2+、TG、TC、HDL及LDL水平明显升高(P〈0.01);urantide组大鼠在给药后,血清中上述各项指标均随给药时间的延长呈现逐渐降低的趋势,达到或接近阳性药组大鼠的水平,与AS模型组比较差异有统计学意义(P〈0.01)。与正常组比较,AS模型组大鼠胸主动脉出现典型AS病变;与AS模型组比较,urantide组大鼠AS病理改变逐渐减轻。与正常组比较,AS模型组大鼠UⅡ及GPR14mRNA的表达水平增高(P〈0.01);与AS模型组比较,urantide组大鼠随给药时间的增加,UⅡ及GPR14mRNA表达水平降低(P〈0.01)。结论:urantide对AS大鼠胸主动脉损伤有一定的保护作用。
Objective To observe the influence of urantide on the injury of thoracic aorta in rats with atherosclerosis ( AS ) and to investigate its mechanism of prevention and treatment of AS.Methods The AS rat model was induced by feeding high fat diet and arterial intimal injury with intraperitoneal injection of vitamin D3,and the rats were randomly divided into normal control group,AS model group,positive medicine group and urantide group;biochemistry was used to detect the levels of serum Ca 2+,triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low density lipoprotein (LDL); hematoxylin-eosin staining was performed to observe the morphogical changes of rat thoracic aorta ; RT-PCR method was used to measure the mRNA expressions of urotensinⅡ (UⅡ) and G protein couple receptor 14 (GPR14) .Results The levels of serum Ca2+,TG,TC,HDL and LDL of the rats in AS model group were significantly higher than those in normal control group ( P 0.01); compared with AS model group,the expression levels of the serum indicators were gradually decreased with the prolongation of time,and reached or approached the serum levels in positive medicine group (P0.01) .The rats in AS model group had the typical AS changes in thoracic aorta ; compared with normal control group,the expression levels of UⅡand GPR14mRNA in AS model group were significantly increased (P0.01); compared with AS model group,the expression levels of UⅡand GPR14mRNA of the rats in urantide group were decreased (P0.01) with the prolongation of time.Conclusion Urantide has significantly protective effect on the injury of thoracic aorta in AS rats.