维生素D3对自发高血压大鼠主动脉环血管内皮依赖的收缩及舒张的影响机制研究  

Effects on Vasomoters after Chronic Treatment with Vitamin D3 in the Aorta of the Spontaneously Hypertensive Rat

作　　者：屈晨[1] 祝岩 Qu Chen;Zhu Yan(Department of Cardiology,Shenyang Medical College Affiliated Central Hospital,Liaoning 110023,China)

机构地区：[1]沈阳医学院附属中心医院,110023 [2]中国人民解放军北部战区总医院心脏血管外科,110016

出　　处：《医学研究杂志》2020年第1期89-93,99,共6页Journal of Medical Research

基　　金：中国博士后科学基金资助项目(2013M542568)。

摘　　要：目的通过观察维生素D 3对高血压状态下血管内皮收缩及舒张的影响和环氧化酶(COX)的信号转导途径的研究,探讨维生素D 3的血管内皮的保护作用机制。方法应用38~42周的雄性自发高血压大鼠(SHR),分为维生素D 3治疗组、对照组,每组20只。维生素D 3治疗组给予维生素D 310ng/(100g·d),灌胃3周;对照组给予蒸馏水灌胃3周,各组每日灌胃前测量大鼠体质量。3周后测血压,留取血液样本,测量一氧化氮(NO)含量。离取主动脉,水浴在10ml的组织浴槽中,通过不同药物及试剂的干预,探测血管张力的变化。采集浴槽内液体及实验后动脉环进行Western blot法分析一氧化氮合成酶的表达及环氧化酶的蛋白表达;ELISA测量内皮因子的释放。结果维生素D 3对自发性高血压病大鼠体质量增长趋势无显著影响。与对照组比较,维生素D 3治疗可显著降低大鼠血管的收缩压及舒张压。治疗组大鼠血液中NO含量明显升高。经过维生素D 3长期治疗后,一氧化氮合成酶的表达增加,环氧化酶-1的表达下降。维生素D 3治疗组血管内皮收缩因子的稳定代谢产物较对照组减少。结论维生素D 3可增加血管舒张因子NO含量,影响一氧化氮的表达,增加血管舒张,降低血管内皮收缩因子的释放,影响环氧化酶-1的表达,长期给药可能通过减少血管内皮收缩因子起到血管保护性作用。Objective The present study investigated whether or not vitamin D 3 protects against vascular dysfunction in hypertension and,if so,whether or not such protection alters the expression of key proteins involved in that dysfunction.Methods We examined the chronic in vivo effect of a physiological dose of vitaminD 3 on the occurrence of endothelium-dependent relaxations and contractions.Spontaneously hypertensive rats(SHR)were treated with the vitamin D 3 for 3 weeks.The decreasing tendency of body weight in control group were revised by long term treatment of vitamin D 3.The arterial blood pressure of the treated SHR was significantly lower than that of control group.Aortic rings with or without endothelium were studied in organ chambers for isometric force measurement.The chronic treatment of vitamin D 3 improved the impaired relaxations.There were no significant differences in contractions evoked by A-23187 between the control and treated groups without the presence of endothelium.Chronic treatment of vitamin D 3 can decrease the contractions in the aortas of SHR in the presence of endothelium.The protein expression level of endothelial nitric oxide synthase(eNOS)and cyclooxygenase-1(COX-1)were studied by Western blot.Results The impaired protein expression of eNOS were restored by the chronic treatment of vitamin D 3.The protein expression studies indicated that the overexpression of COX-1 observed in SHR aorta was reduced by the chronic treatment of vitamin D 3.Elisa kit analyses showed the metabolites of endothelium dependent conctrating factors were decreased by chronic vitamin D 3 treatment.Conclusion These results demonstrate that chronic treatment with vitamin D 3 modulates vascular tone by augmentation of relaxation and reduction in endothelium-dependent contractions.This modulation is accompanied by a lowered blood pressure,reduced expression of COX-1 protein,and increased eNOS level in SHR.The present findings suggest that vitamin D 3 is effective in preserving endothelial function in hypertension.

关 键 词：维生素D 3 血管内皮舒张因子 血管内皮收缩因子 高血压 

分 类 号：R966[医药卫生—药理学]