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  

Correlation analysis of epoxyeicosatrienoic acids with vascular endothelial dysfunction in senile diabetes mellitus

作　　者：黄亚莉[1] 汪燕[1] 邓宪[1] 沈若宇[1] 吴玲[1] 陆彤 

机构地区：[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

出　　处：《第二军医大学学报》2011年第3期271-275,共5页Academic Journal of Second Military Medical University

基　　金：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]~~

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。Objective To 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. Methods We 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. Results Compared 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. Conclusion Our 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.

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 

分 类 号：R587.1[医药卫生—内分泌]