毒死蜱下调内皮型一氧化氮合酶的表达降低了脑基底动脉内皮依赖性舒张功能  

Chlorpyrifos Downregulates Endothelial Nitricoxide Synthase Expression and Decreases Endothelium Dependent Relaxation of Basilar Arteries

作　　者：刘锋[1] 周寿红[2] 梁江红[1] 

机构地区：[1]南华大学附属第二医院神经内科,湖南省衡阳市421001 [2]南华大学医学院生理学教研室,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2010年第5期371-374,共4页Chinese Journal of Arteriosclerosis

摘　　要：目的探讨毒死蜱对血管舒张功能的影响及其可能的机制。方法采用离体血管环灌流方法,观察不同浓度的毒死蜱预处理对新西兰兔脑基底动脉环对乙酰胆碱和硝普钠介导的舒张反应以及血管组织中一氧化氮含量的影响。同时,观察不同浓度的毒死蜱预处理对培养的人脐静脉内皮细胞培养液中一氧化氮含量和内皮型一氧化氮合酶表达的影响。结果毒死蜱（0.001~0.1 mmol/L）预处理30 min,浓度依赖性地抑制乙酰胆碱诱导的内皮依赖性舒张反应和降低了血管组中一氧化氮的含量,而对硝普钠引起的非内皮依赖性舒张反应没有影响。阿托品预处理则不影响毒死蜱的作用。毒死蜱（0.001~0.1 mmol/L）预处理30 min,浓度依赖性降低了培养液中一氧化氮的含量和内皮型一氧化氮合酶的表达。结论毒死蜱能降低血管内皮依赖性舒张反应,其机制可能与毒死蜱下调内皮型一氧化氮合酶的表达,减少一氧化氮的生成,损伤内皮细胞的功能有关。Aim To investigate the effect of chlorpyrifos on relaxation function of artery and explore the potential mechanism. Methods Organ baths in basilar aortic rings of New Zealand rabbits were used to investigate the effect of different concentration chlorpyrifos on vascular relaxation function induced by acetylcholine（Ach） and sodium nitroprusside（SNP）. The level of nitric oxide（NO） was measured in basilar artery and cultural human umbilical vein endothelial cells.The expression of endothelial nitricoxide synthase（eNOS） was detected by Real-time PCR and Western blot in cultural human umbilical vein endothelial cells（HUVEC）. Results Endothelium dependent relaxation and NO content of rabbits basilar aortic rings were decreased in concentration-dependent manner by pre-treatment with chlorpyrifos（0.001 mmol/L,0.01 mmol/L,0.1 mmol/L） for 30 minutes. But chlorpyrifos had no effect on SNP-induced endothelium-independent relaxation of basilar aortic rings.Pre-treatment with atropine had no influence on the action of chlorpyrifos.The level of NO in culture medium and the expression of eNOS in HUVEC were decreased by pre-treatment with chlorpyrifos（0.001 mmol/L,0.01 mmol/L,0.1 mmol/L） for 30 minutes in concentration-dependent manner. Conclusion Chlorpyrifos decreases endothelium dependent relaxation of basilar aortic rings,which the mechanisms may relate to down-regulating of eNOS and decrease of NO induced by chlorpyrifos.

关 键 词：毒死蜱 基底动脉 内皮细胞 一氧化氮 内皮型一氧化氮合酶 

分 类 号：R994.6[医药卫生—毒理学]