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环氧二十碳三烯酸与老年糖尿病血管内皮舒张功能障碍的相关性
黄亚莉1,汪燕1,邓宪1,沈若宇1,吴玲1,陆彤2*
0
(1. 解放军411医院干部病房科,上海 200081; 2. Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN5905, USA)
摘要:
目的比较观察老年糖尿病(DM)、老年糖尿病肾病(DN)和健康老年人之间血清14,15-环氧二十碳三烯酸(14,15-EET)的代谢产物14,15-双羟二十碳三烯酸(14,15-DHET)的含量变化,并分析与血管内皮舒张功能障碍的相关性。方法196例志愿者和患者分为3组:健康老年人组(A组)60例、老年DM组(B组)78例和老年DN组(C组)58例,每组男、女匹配。应用酶联法检测3组血清中14,15-DHET、前列环素(PGI2)代谢产物6-keto-PGF1α和血栓素TXA2代谢产物TXB2的含量,同时检测血糖、血脂等生化指标。采用彩色多普勒超声仪对肱动脉基础内径、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B组和C组分别与A组比较: (1)血清14,15-DHET和6-keto-PGF1α含量下降(P<0.01),TXB2含量升高(P<0.01);(2)TXB2/6-keto-PGF1α比值和TXB2/14,15-DHET比值升高(P<0.01);(3)糖化血红蛋白(HbA1c)、三酰甘油(TG)和总胆固醇(TC)、尿白蛋白排泄量 (UAE)均升高(P<0.01);(4)EDV和NEDV降低(P<0.01)。(5)14,15-DHET含量与DM病程、HbA1c、UAE、TXB2、TXB2/6-keto-PGF1α比值和TXB2/14,15-DHET比值负相关,与EDV和NEDV正相关。结论老年DM和老年DN患者血清中血管内皮依赖性的舒血管因子代谢产物14,15-DHET含量下降发生在DM早期阶段。与PGI2一样,14,15-DHET含量变化可作为判断DM、DN相关的血管EDV和NEDV功能受损的重要指标之一。
关键词:  糖尿病;环氧二十碳三烯酸;细胞色素P-450环氧酶  血管内皮
DOI:10.3724/SP.J.1008.2011.0271
投稿时间:2010-12-28修订日期:2011-03-02
基金项目:南京军区医学科技创新课题 (联卫08A006), 上海市虹口区卫生局重点科研项目\[0802-08(2008)98\].
Correlation analysis of epoxyeicosatrienoic acids with vascular endothelial dysfunction in senile diabetes mellitus
HUANG Ya-li1, WANG Yan1,DENG Xian1,SHEN Ruo-yu1,WU Ling1, LU Tong2*
(1. Carder’s Ward, No. 411 Hospital of PLA, Shanghai 200081, China ; 2. Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN55905, USA)
Abstract:
ObjectiveTo compare the serum contents of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a stable metabolite of epoxyeicosatrienoic acids (EETs), between senile diabetic patients with and without nephropathy and healthy controls, and to analyze the relationship of their contents with vascular endothelial dysfunction. MethodsWe conducted a case control study, which included 60 healthy senior citizens (group A), 78 senior diabetic patients with no clinical evidence of nephropathy (group B), and 58 senior diabetic nephropathy patients (group C). Serum levels of 14,15-DHET, 6-keto-PGF1α (a stable metabolite of prostaglandin) and TXB2 (a stable metabolite of thromboxane A2) were measured using ELISA kits. Meanwhile, the parameter of blood glucose and lipid were also examined. The endothelium-dependent vasorelaxation (EDV) and non-endothelium-dependent vasorelaxation (NEDV) in the brachial arteries were determined by Color Doppler Ultrasound. ResultsCompared with group C, group A and B had significantly lower serum levels of 14, 15-DHET and 6-keto-PGF1α , and values of EDV and NEDV(P<0.01), and had significantly higher levels of blood hemoglobin A1c (HbA1c), triglyceride, cholesterol, and TXB2 , urine protein albumin, and values of TXB2/6-keto-PGF1α and TXB2/14,15-DHET(P<0.01). The level of 14,15-DHET was negatively correlated with the course of disease, the levels of HbA1c, TXB2, triglyceride and cholesterol, and the ratios of TXB2/6-keto-PGF1α and TXB2/14,15-DHET; and it was positively correlated with the values of EDV and NEDV in senile diabetic patients with and without nephropathy. ConclusionOur results indicated that serum 14,15-DHET level is decreased during the early stage of senile diabetic patients with and without nephropathy. Like PGI2, 14,15-DHET may also serve as a biomarker for the impairment of EDV and NEDV in senile diabetic patients with and without nephropathy.
Key words:  diabetes mellitus  epoxyeicosatrienoic acids  cytochrome P-450 epoxygenase  vascular