过氧化物酶体增殖物激活受体双重激动剂WY14643长期给药对血管内皮的保护机制研究  

The Beneficial Effect of Chronic Treatment with Dual Peroxisome Proliferator-activated Receptor Agonist WY14643 on Vascular Endothelium

作　　者：屈晨[1] 祝岩[2] QU Chen;ZHU Van(Department of Cardiology,Shenyang Medical College Affiliated Central Hospital,Shenyang 110023,China;Department of Cardiac Surgery,Ceneral Hospital of Shenyang Military Region,Shenyang 110016,China)

机构地区：[1]沈阳医学院附属中心医院循环科,沈阳110023 [2]沈阳军区总医院心脏血管外科,沈阳110016

出　　处：《临床误诊误治》2018年第10期93-97,共5页Clinical Misdiagnosis & Mistherapy

基　　金：中国博士后科学基金(2013M542568)

摘　　要：目的通过观察过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptors,PPAR)双重激动剂WY14643对高血压状态下血管内皮收缩因子和环氧化酶信号转导途径的影响,探讨其抗血管收缩及降压保护作用机制。方法选择雄性38~42周的自发性高血压病大鼠(SHR) 40只分为SHR治疗组、SHR对照组各20只,另选取雄性38~42周WKY大鼠20只作为WKY组。SHR治疗组给予WY14643 50 mg/kg灌胃3周,SHR对照组及WKY组给予蒸馏水对照灌胃3周。3周后各组测血压,留取血液样本检测一氧化氮(NO)含量。离取主动脉,在10 ml的组织水浴槽中通过不同药物及试剂干预,探测血管张力的变化。采集浴槽内液体及实验后动脉环采用酶联免疫吸附法及蛋白质免疫印迹法分析血管内皮收缩因子和环氧化酶-1的表达情况。结果与SHR对照组相比,SHR治疗组血压下降,NO含量升高,差异有统计学意义(P <0. 01); SHR治疗组血压和NO水平与WKY组一致(P>0. 05)。SHR治疗组血管收缩率较SHR对照组降低(51±5)%(P <0. 05),WKY组无明显血管收缩;在有血管内皮存在的基础上环氧化酶-1表达明显减少(P <0. 05),在无血管内皮存在的基础上环氧化酶-1表达无区别(P>0. 05)。SHR治疗组前列腺素F1α、前列腺素F2α和血栓素A_2的释放明显减少(P <0. 05); SHR对照组前列腺素F1α、前列腺素F2α和血栓素A_2的释放情况与WKY组相似(P>0. 05)。结论 PPAR双重激动剂WY14643可增加血管舒张因子NO含量,影响环氧化酶的表达,长期给药可能通过减少血管内皮收缩因子起到降压保护作用。Objective The present study aimed to determine the effect of＂ du＇onic treatment with dual paroxysm proliferator-activated receptor （PPAR） agonist, WYlz-43, on vascular endothelium-derived contraction factor and Cycloox ygenase （COX） signal transduction pathway in hypertensive state, and to explore its anti-vasoconstriction and antihypertensire mechanism involved. Methods Folly male spontaneously hypertensive rats （SHR） aged 38-42 weeks were divided into SHR treatment group （n = 20） and SHR control group （n = 20）. Another 20 male WKY rats aged 38-42 weeks were se- lected as WKY group. SHR treatment group was fed with WY14643 50 mg/kg by gastric lavage for 3 weeks. SHR control group and WKY group were fed with distill water by gastric lavage for three weeks. Then blood pressure （BP） was meas- ured, and blood samples were collected to detect the content of NO. The aorta was removed and the changes in vascular tone were detected by intervention of different diugs and reagents in a 10 ml tissue water bath. The fluid in the bath and isolated aortic rings were collected to analyze the expression of EDCF and COX-1 by Elisa and Westem Blot. Results BP was decreased, while NO release was increased in SHR treatment group, as compared with SHR control group（P 〈0.01 ）. BP and NO level in SHR treatment group were consistent with those in WKY group. As compared with SHR control group, endothelium-dependent contractions were reduced in SHR treatment group （51 _＋ 5 ）% （P 〈 0.05 ）. The expression ofCOX-1 was significantly decreased in the presence of vascular endotheliun-l （P 〈 0.05）, and there was no difference in the expression of COX-1 in the absence of vascular endothelium （ P 〉 0. 05 ）. The release of PGFlot, PGF2ot and thromboxane A2 in SHR treatment group were significantly decreased （P 〈 0.05 ）, whereas the release of those indicators in SHR control group were similar to those in WKY gaoup （P 〉 0.05）. Conclusion Dual PPAtt agonist WY14643 has the ability

关 键 词：过氧化物酶体增殖物激活受体 血管内皮收缩因子 

分 类 号：R-332[医药卫生] R593.23