过氧化物酶体增殖物激活受体双重激动剂WY14643对血管内皮的保护研究  

Study on the beneficial effect of dual peroxisome proliferator-activated receptor agonist WY14643 onvascular endothelium

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

出　　处：《中国医师杂志》2012年第6期746-749,共4页Journal of Chinese Physician

摘　　要：目的通过研究过氧化物酶体增殖物激活受体（PPAR）双重激动剂WYl4643对高血压状态下血管内皮收缩因子和COX的信号转导途径的影响，探讨双重PPAR激动剂的抗高血压保护作用机制。方法实验应用38-42周的雄性自发高血压大鼠（SHR）离取胸主动脉环，水浴在10ml的组织浴槽中，通过不同药物及试剂的干预，探测血管张力的变化。采集浴槽内液体及实验后动脉环进行ELISA及Westernbla分析内皮因子的释放和环氧化酶的蛋白表达。结果10．0μmol／LWY14643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=0．014）；PPARa拮抗剂MK866可以明显提高10．0μmol／LWY14643孵育SHR大鼠的血管收缩能力（P=0．021），PPARγ／拮抗剂GW9662对10．0μmoL／LWY14643孵育SHR大鼠的血管收缩能力没有显著影响（P=0．061）。与对照组相比，10mmol／LWY14643组SHR大鼠离体主动脉释放的PGF10a（P=0．012）、2a（P=0．019）和TXB2（P=0．023）水平明显降低。在血管内皮存在的前提下，WY14643处理组SHR大鼠的COX-1表达较未给予WY14643处理的SHR大鼠明显降低（P=0．017）。结论PPAR双重激动剂WY14643影响环氧化酶的表达，PPAR双重激动剂可能通过减少血管内皮收缩因子起到降压保护性作用。Objective The present study aimed to determine whether or not dual paroxysm prolifer- ator-activated receptor （PPAR） agonist, WY14643, improved the dysfunctioned vascular endothelium in hypertension by reducing endothelium-derived contracting factors （EDCFs）, and to explore the molecular mechanism it was involved in. Methods Isometric tension in isolated thoracic aortic rings of spontaneously hypertensive rats was recorded. Endothelium-dependent contractions evoked by acetylcholine in the presence of L NAME were reduced by fenofibrate. Cyclooxygenase 1 （ COX1 ） activities were determined, by analyzing the peroxidase activity of cyclooxygenase colorimetrically by using ELISA kit. Results Compared to the control group, WY14643 significantly decreased the vasoconstriction in aorta of the SHR rats（ P = 0. 014）. PPARot antagonist MK866 enhanced the vascular contractility of SHR rats that were incubated with 10.0 μmol/L WY14643 （ P = 0. 021 ）. PPARγ antagonist GW9662 did not significantly affect the vascular con- tractility of SHR rats that were incubated with 10. 0 μmol/L WY14643 （ P = 0. 061 ）. The levels of serum PGF1a（ P =0. 012）, 2ct（ P =0. 019） and TXB2（ P =0. 023） in SHR rats incubated with 10.0 μmol/L WY14643 were significantly lower than the control group, respectively. Under the condition of the existence of vascular endothelium, the expression of COX-1 in SHR rats incubated with WY14643 was significantly lower than that in SHR rats incubated without WY14643 （ P = 0. 017）. Conclusions Those data showed that WY14643 reduced the release of EDCFs, it suggests that WY14643 protects against vascular diseases through the PPAR activators in spontaneous hypertension.

关 键 词：过氧化物酶体增殖物激活受l体/激动剂 环氧化酶1/代谢 内皮缩血管肽类/代 谢 高血压 大鼠 

分 类 号：R285.5[医药卫生—中药学]