菲诺贝特对高血压大鼠血管内皮收缩因子分泌的影响及其作用机制  

Effect of Fenofibrate on the Secretion of Endothelium-derived Contracting Factors in Hypertensive Rats

作　　者：屈晨[1] 唐亮[1] 祝岩[2] 

机构地区：[1]沈阳医学院奉天医院循环内科,沈阳110024 [2]沈阳军区总医院心脏外科,沈阳110016

出　　处：《中国医学科学院学报》2012年第3期239-243,共5页Acta Academiae Medicinae Sinicae

摘　　要：目的观察过氧化物酶增殖活化受体α(PPARα)激动剂菲诺贝特对高血压大鼠血管内皮收缩因子分泌的影响,探讨其作用机制。方法采用血管环收缩实验观察用0.1、1.0、10.0μmol/L菲诺贝特及10.0μmol/L菲诺贝特与PPARα拮抗剂MK866和PPARγ拮抗剂GW9662孵育1 h后SHR大鼠血管张力的变化情况,并与WKY大鼠进行比较;酶联免疫吸附试验(ELISA)测定血管内皮收缩因子前列环素(PGF)1α、2α和血栓素B2(TXB2)的分泌情况;Western blot检测COX-1蛋白的表达情况。结果 10.0μmol/L菲诺贝特可以明显降低SHR大鼠的血管收缩能力,与对照组相比差异有统计学意义(P=0.013);PPARα拮抗剂MK866可以明显提高10.0μmol/L菲诺贝特孵育SHR大鼠的血管收缩能力(P=0.021),PPARγ拮抗剂GW9662对10.0μmol/L菲诺贝特孵育SHR大鼠的血管收缩能力没有显著影响(P=0.071)。与对照组相比,10 mmol/L菲诺贝特组SHR大鼠离体主动脉释放的PGF1α(P=0.014)、2α(P=0.023)和TXB2(P=0.017)水平明显降低。在血管内皮存在的前提下,菲诺贝特处理组SHR大鼠的COX-1表达较未给予菲诺贝特处理的SHR大鼠明显降低(P=0.027)。结论菲诺贝特可以减少高血压大鼠血管内皮收缩因子的分泌,其可能是通过影响内皮对COX-1的表达来实现的。Objective To evaluate the effect of peroxisome proliferator-activated receptor （PPAR） α agonist fenobibrate on the secretion of endothelium-derived ontracting factors in hypertensive rats. Methods The changes of vascular tension in SHR rats after having been incubated with 0. 1, 1.0, or 10.0μmol/L feno- bibrate or 10.0μmol/L fenobibrate and PPARα antagonist MK866 or PPARα/antagonist GW9662 for one hour were observed, and the findings were compared with those in WKY rats （control group）. The serum levels of vascular endothelial contraction factor prostacyclin （PGF） lα, 2α, and thromboxane B2 （TXB2） were deter- mined by enzyme-linked immunosorbent assay （ELISA）. The expression of COX-1 protein was determined byWestern blot analysis. Results Compared with the control group, fenobibrate significantly reduced the vaso- constriction ability of the SHR rats （P = 0.013 ）. PPARa antagonist MK866 significantly improved the vascu- lar contractility of SHR rats that had been incubated with 10.0μmol/L fenobibrate （P = 0. 021 ）. PPARα an- tagonist GW9662 had no significant effect on the vascular contractility of SHR rats after having been incubated with 10.0μmol/L fenobibrate （ P = 0. 071 ）. The serum levels of PGF1 α（ P = 0. 014 ）, 2or （ P = 0. 023 ）, and TXB2 （P = 0. 017 ） in SHR rats incubated with 10.0μmol/L fenobibrate were significantly lower than in the control group. With the presence of vascular endothelium, the expression of COX-1 in SHR rats incubated with fenobibrate was significantly lower than that in SHR rats incubated without fenobibrate （ P = 0. 027 ）. Conclusion Fenobibrate reduces the secretion of endothelium-dependent contracting factors in SHR rats through lowering the expression of COX-1.

关 键 词：过氧化物酶增殖活化受体α 菲诺贝特 血管内皮收缩因子 环氧化酶 

分 类 号：R544.1[医药卫生—心血管疾病]