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目的动态、系统地观察家兔实验性动脉粥样硬化(AS)进程中内皮功能的变化及垂体腺苷酸环化酶激活肽(PACAP)的干预作用。方法新西兰雄性家兔60只,随机等分为两组AS模型组(AS组)及PACAP干预组(干预组)。分别于实验的第0、2、4、8、12周末测定血脂、血清一氧化氮(NO)含量及一氧化氮合酶(NOS)活性,同时处死每组兔5～6只,取其胸主动脉做形态学观察。结果①AS组4周末时内皮细胞(EC)出现脱落;4周末后NO及cNOS活性有所增高,最终两者呈总体下降的趋势;iNOS活性8周末前持续上升,其后下降。②干预组EC形态改变出现较晚;12周末时NO含量及4周末时cNOS活性、2周末时iNOS活性均高于AS组(P<0.05)。结论AS进程中NO水平及NOS活性是一个不断变化的动态过程,PACAP可通过提高NOS活性等途径增加血清NO含量,保护EC,这可能是PACAP抗AS的重要机制之一。
Objective To observe the change of endothelial function and the effect of pituitary adenylate cyclase activating protein (PACAP) during the process of experimental atherosclerosis (AS) in rabbits. Methods Sixty New Zealand male rabbits were randomly divided into two groups: AS model group (AS group) and PACAP intervention group (intervention group). Blood lipids, serum nitric oxide (NO) and nitric oxide synthase (NOS) activity were measured at the 0, 2, 4, 8, and 12weeks of the experiment respectively. Aortic morphology was observed. Results ① The endothelial cells (ECs) were shed at the end of the 4th week in the AS group. NO and cNOS activity increased at the end of the 4th week, and eventually both showed an overall decreasing trend. The iNOS activity continued to increase before the end of the 8th week and then decreased. ② The changes of EC morphology appeared later in the intervention group. The content of NO and the activity of cNOS at the end of the 4th week were higher than that of the AS group at the end of the 12th week (P <0.05). Conclusions The level of NO and the activity of NOS in AS process are a dynamic process. PACAP can increase serum NO level and protect EC through increasing NOS activity, which may be one of the important mechanisms of PACAP anti-AS.