Agr-related changes in vascular endothelial cell functions

用年轻(5周龄)、成年(40-50周龄)和老年(100-110周龄)大鼠评估血管内皮细胞功能的年龄相关性变化。方法：1.培养内皮细胞的分离：取青年和老年大鼠的胸主动脉和末梢动脉，采用组织块法分离内皮细胞，至少可以培养到第20代。细胞增殖和迁移：发展了一种新的、简单的测量内皮细胞迁移的方法。随着大鼠增龄，内皮细胞~(3 H)-胸腺嘧啶核苷的掺入减少，细胞迁移减少。血小板聚集和血小板/主动脉前列腺素样物质的产生：ADP诱导的血小板聚集随着年龄的增长而增加。血小板和主动脉/主动脉内皮细胞的TXA_2水平随增龄而升高，导致血小板聚集指数(血小板TXA_2浓度/主动脉PGI_2生成量)随增龄而升高。血管内皮源性收缩和松弛…的产生更多的G因子：随着年龄的增长，大鼠尾动脉内皮细胞分泌Endotheline-1增加，而对乙酰胆碱的内皮依赖性松弛反应和从尾动脉或内皮细胞释放的嘌呤类化合物减少。这些递增和递减会导致大鼠血压随着年龄的增长而升高。一氧化氮(NO)电极的研制：与InterMedical Co.Ltd.合作开发了一种NO电极，该电极可以检测到经卡巴胆碱处理后的主动脉释放出的10℃-8~gt；M NO的存在。组织块法分离的大鼠血管内皮细胞的生理和病理生理功能的测定被证实是阐明与人类衰老相关的血管疾病发生机制的有用方法。本研究还证实了血管疾病的发生与年龄相关的内皮细胞功能障碍之间存在着密切的关系。较少

Age-related changes in vascular endothelial cell functions were estimated using young (5 weeks old), adult(40-50 weeks old)and old(100-110 weeks old)rats.Results and Conclusion1. Isolation of cultured endothelial cells(ECs) : From thoracic aorate and cadual arteries of young and old rats, endothelial cells were isolated by an explant method and could be cultured at least until the 20th passage.2. Cell proliferation and migration : A new and simple method for measureing the migration of ECs was developed. Both the incorporation of ^3H-thymidine into ECs and migration of the cells decreased with rat aging.3. Platelet aggregation and platelet / aortic prostanoid production : ADP-induced platelet aggregation increased with rat aging. TXA_2 levels of platelet and aortic / tha aortic ECs increased with aging, inducing increment in an index of platelet aggregation(platelet TXA_2 concentration / aortic PGI_2 production)with rat aging.4. Production of endothelium-derived contracting and relaxin … More g factors : Endotheline-1 secretion from caudal ECs increased with rat aging, while the endothelium-dependent relaxing response to acetylcholine and release of purine compounds from the caudal artery or the ECs decreased. These increments and decrements would induce an increase in blood systolic pressure with rat aging.5. Development of nitric oxide(NO)electrode : By collaborating with Intermedical Co.Ltd., a NO electrode was developed and the presence of 10^<-8>M NO, which is released by treatment of aortae with carbachol, could be detected by using the electrode.The measurement of the physiological and pathophysiological functions of rat vascular endothelial cells which were isolated by the explant method was confirmed to be a useful methods to elucidate the mechanisms of occurrence of vascular disease associated with human aging. From the present study, close relationships were also confirmed to exist between the occurrence of vascular disease and age-related dysfunction of endothelial cells. Less