高尿酸血症对血管内皮细胞功能损伤的机制研究

摘要

Objective To investigate the mechanism of vascular endothelial cells (VEC) function injury when suffering Hyperuricemia (HUA).Methods Using self-control animal experiments,sustained hyperuricemia models were reproduced by gavaging potassium oxonate.The experimental indicators were determined after collecting blood respectively through venous plexus in rat eye.Blood was collected through venous plexus 0,5,10,15,20 days after administration.Then,the level of uric acid,NO and iNOS were determined.Blood samples were taken from heart 20 days after administration,centrifuged,and the supernatant was collected.Then,abdominal aorta and kidneys were performed with HE staining,whether producing tissue urate crystals was observed,Human umbilical vein endothelial cells suffered primary culture,while hyperuricemia serum underwent intervention culture.The NO contents in cell supernatant were detected.Results As the modeling time continued,the blood uric acid levels increased significantly especiallyon the 5th,15thday after administration (P＜0.05).At the same time,the serum content of NO and iNOS level were reduced with duration.Scattered urate crystals were not found in abdominal aorta and kidney.The NO level in endothelial cells decreased after human umbilical vein endothelial cells were intervened by high serum uric acid of rats.Conclusion The hyperuricemia was time-dependent,which can sustainably damage vascular endothelial cells,reduce the function of vascular endothelial cell,and increase the risk of cardiovascular disease.%目的 探讨高尿酸血症对血管内皮细胞功能损伤的机制.方法 采用自身对照动物实验,通过灌胃氧嗪酸钾来复制持续高尿酸血症大鼠模型,分别通过对大鼠眼球后静脉丛取血测定实验指标,给药第0、5、10、15、20天对大鼠眼球后静脉丛取血,进行尿酸、NO、iNOS测定,其中第20天对实验大鼠进行心脏取血,离心取上清液.取血完后取腹主动脉和肾脏进行HE染色,观察是否产生组织尿酸盐晶体;原代培养人脐静脉内皮细胞,高尿酸血清干预培养,检测细胞上清液中NO含量.结果 随着造模时间的持续,大鼠血尿酸含量呈增加趋势(P＜0.05),尤其第5、15天血尿酸含量明显增加(P＜0.05),同时血清中NO、iNOS含量均随着时间持续而有所降低,HE染色腹主动脉和肾脏未发现尿酸盐晶体散在;人脐静脉内皮细胞经大鼠血清高尿酸血清干预后,内皮细胞NO含量降低.结论 高尿酸血症呈时间依赖性,可持续性地损伤血管内皮细胞,降低血管内皮细胞功能,增加心血管病发生风险.