花生四烯酸细胞色素P450表氧化酶代谢产物与健康老年人血管内皮舒张功能障碍的相关性

Relationship of cytochrome P-450 epoxygenase metabolites of arachidonic acid with impaired endothelium -dependent vasorelaxation in the healthy elderly

目的检测健康老年人血清环氧二十碳三烯酸（Epoxyeicosatrienoic acids，EETs）代谢终产物的含量变化，分析其与血管内皮舒张功能的相关性。方法120例志愿者按年龄分为青年组60例和老年组60例，每组男、女各30例。应用酶联法检测两组血清中14，15-环氧二十碳三烯酸代谢终产物14，15双羟二十碳三烯酸（14，15-DHET）、前列环素终产物6酮-前列腺素F1α（6-Kote—PGF1α）和血栓素终产物血栓素B2（TXB2）的含量，同时检测血糖、血脂等生化指标。采用超声对肱动脉基础内径、血管内皮依赖性舒张功能（EDV）和硝酸甘油介导的血管内皮非依赖性舒张功能（NEDV）进行测定。结果与青年组比较，老年组糖化血红蛋白（HbAlc）、三酰甘油和胆固醇增高（P〈0．01）；血清14，15-DHET和6-Kote—PGF1α含量明显下降（P〈0．01），TXB2／6-Kote—PGF1α（T／P）比值和TXB2/14，15-DHET（T／D）比值升高（P〈0．01）；肱动脉基础内径增宽（P〈0．05），EDV和NEDV明显降低（P〈0．01）。14，15-DHET含量与年龄和T／D比值呈负相关，与EDV正相关。结论健康老年人血清中血管内皮依赖性的舒血管因子终产物14，15-DHET及6-Kote—PGF1α含量均下降，可能与内皮花生四烯酸细胞色素P450表氧化酶及脂环氧酶的代谢产物生成减少有关，是衰老相关的血管EDV和NEDV功能受损的重要参考指标。

Objective To determine the relationship of cytochrome P-450 epoxygenase metabolites of arachidonic acids with impaired endothelium-dependent vasorelaxation in the healthy elderly. Methods A case-control study was employed. The study enrolled 60 healthy young adults （group A） and 60 healthy senior citizens （group B） of Han population in Shanghai. Serum contents of 14,15 dihydroxyeicosatrienoic acid （14, 15-DHET） （a stable metabolite of 14,15-EET）, 6-Kote- PGFla （a stable metabolite of prostaglandin） and TXB2 （a stable metabolite of thromboxane A2） were measured using EI.ISA kits. The endothelium-dependent vasorelaxation （EDV） and endothelium- independent vasorelaxation （NEDV） in brachial arteries were determined by color Doppler ultrasound. Results Compared with group A, group B had significant higher levels of hemoglobin Alc, triglyceride and cholesterol levels （P〈0.01）, and significant lower levels of 14,15-DHET and 6-Kote PGFla （P〈0. 001）, leading to increased values of TXB2/6-Kote-PGFla and TXB2/14,15 DHET. There was bigger basal interior diameter of brachial arterials with reduced EDV and NEDV response （P〈0.01 and P〈0. 05, vs. group A respectively） in group B. Moreover, the age was negatively correlated with 14,15 DHET and TXB2/14,15-DHET. Conclusions Our results indicate that the impaired EDV and NEDV in aging are associated with reduced production of arachidonic acid metaboliles lhrough cytochrome P-450 epoxygenase pathway and cyooxygenase pathway of endothelium in the healthy elderly.