PPAR-α激动剂对大鼠内皮功能不全的作用及机制探讨  

Effects of PPAR-α Ligands on Endothelial Dysfunction in Rats and the Mechanism of Therapy

作　　者：康奕飞[1] 何兆初[1] 吴竣[1] 曾昭华[1] 

机构地区：[1]广州医学院第一附属医院心血管内科,广州市510120

出　　处：《医学理论与实践》2008年第6期621-624,共4页The Journal of Medical Theory and Practice

基　　金：广东省自然科学基金(0400870)

摘　　要：目的:观察PPAR-α激动剂对高脂血症模型大鼠内皮功能不全的作用,并初步探讨其作用机制。方法:称重后,32只SD雄性大鼠随机分成4组,每组8只:正常对照组(A组);正常+非诺贝特治疗组(B组);高脂组(C组);高脂+非诺贝特治疗组(D组)。每周称体重,按体重调整饲料及药物量。12周后,分别检测血脂4项(TC、TG、LDL-c、HDL-c)及血清中NO含量。分离胸主动脉,检测组织匀浆中总NOS活性及离体血管环的舒缩功能。结果:在调脂方面,PPAR-α激动剂非诺贝特能显著降低TG,并能在一定程度上降低LDL,同时显著升高HDL的作用。此外,PPAR-α激动剂非诺贝特具有显著增加总NOS活性及升高NO含量的作用,能显著改善内皮依赖性舒张功能,其作用并不完全依赖于血脂的降低。结论:PPAR-α激动剂非诺贝特能显著增加总NOS活性从而升高NO含量及改善血管内皮依赖性舒张功能,对内皮功能不全起到预防及治疗的作用,这可能是来自于调脂以外的作用。Objective： To investigate effects of PPAR-α ligands on endothelial dysfunction in hyperlipoidemia rats and the mechanism of fenofibrate therapy. Methods：After weighed, thirty-two male SD rats were divided randomly into four groups： normal diet control group（group A）~ normal diet＋fenofibrate therapy（group B）; Hyperlipid diet group（group C） and Hyperlipid diet＋fenofibrate therapy group（group D）. These animals were weighed at every week and the quantity of animal feeds and drugs was adjusted. After twelve weeks, the blood samples were drawn in order to measure plasma lipids（including TC,TG,LDL-c, HDL-c） and serum NO level. Then the rats were killed, thoracic aortas were taken for observation of vasodilator and vasoconstrictor activity in response and detection NOS. Results： Fenofibrate could remarkably decrease plasma TG level, to a certain extent reduce plasma LDL level, and remarkably increase plasma HDL level. Furthermore, Fenofibrate could evidently increase serum NO and tissular NOS, and observably improve the thoracic artery endothelium-dependent vasodilator activity in response to acetylcholine in vitro. However, prove the effects of fenofibrate were only partially correlated with changes in plasma lipids and lipoproteins. Conclusion：Fenofibrate can evidently increase serum NO and tissular NOS, and observably improve the thoracic artery endothelium-dependent vasodilator activity in response to acetylcholine in vitro. The effects of fenofibrate may be independent of the decreased of plasma lipids.

关 键 词：高脂血症 内皮功能不全 PPAR-α激动剂 一氧化氮 一氧化氮合酶 

分 类 号：R543[医药卫生—心血管疾病]