摘要
目的:观察大气环境中细颗粒物对血管内皮功能的影响,探索细颗粒物作用于心血管疾病的途径和机制,同时使用阿托伐他汀进行干预,观察药物对内皮损伤的作用。方法:将细颗粒物使用0.9%氯化钠配制成浓度为4000μg/ml的悬浮液,对人脐静脉血管内皮细胞(Endothelial cells,EC-304)进行染毒,染毒终浓度为400μg/ml,观察细颗粒物对EC-304细胞存活率、细胞内丙二醛(Malondial dehyde,MDA)、细胞裂解液中超氧化物歧化酶(Superoxide dismutase,SOD)及细胞上清液中一氧化氮(Nitrous oxide,NO)等的影响。同时使用阿托伐他汀钙药物进行干预,在染毒细胞中加入0.1μmol/L,1μmol/L和10μmol/L剂量浓度的阿托伐他汀钙,测定药物对上述指标的影响。结果:细颗粒物有机提取物染毒后,EC-304的存活率明显下降、细胞上清液MDA明显升高、细胞内SOD及细胞上清液中NO较对照组明显下降(P<0.01)。染毒后加入阿托伐他汀钙能明显改善细颗粒物对血管内皮细胞的毒性作用,使EC-304上清液MDA较对照组明显下降,而细胞存活率、细胞内SOD及细胞上清液中NO较对照组增加,并有剂量-反应关系(P<0.01)。结论:细颗粒物对EC-304具有明显的损害作用,环境因素如细颗粒物在心血管疾病的发生发展中起着不可忽视的作用,同时使用他汀类药物可以改善血管内皮功能,促进心血管疾病的功能恢复,论证了他汀类药物可改善细颗粒物导致血管内皮损伤的药理作用。
Objection:To observe the effects of ambient fine particles on cardiovascular endothelial functions and to explore the toxicological mechanisms on cardiovascular system. Additionally,drug intervention of statin was performed to verify the potential toxicological mechanisms of fine particles on human umbilical vein endothelial cells.Method:Ambient fine particles were prepared for density of 4000μg/ml with formulation of 0.9% Nacl. EC-304 cells were exposed to 400μg/ml dose organic extracts. Cell activity and the levels of malondialdehyde (MDA),Nitrous oxide (NO) and Superoxide dismutase (SOD) in EC-304 cells were detected in the experiments. Moreover,EC-304 were exposed to the 400 μg/mL organic extracts of fine particles followed by the intervention of astorvastatin in concentrations of 0.1 μmol/L,1 μmol/L and 10 μmol/L,respectively. Results The results showed that MDA increased significantly after exposed to organic extracts of fine particle,but cell activities,SOD and NO in EC-304 cells decreased significantly,Meanwhile,in comparison with the group of cells with no atorvastatin group,the levels of MDA obviously decreased after the addition of atorvastatin,while cell activities,SOD and NO levels apparently increased,that showed in a dose dependent manner.Conclusion:The results indicated that endothelial dysfunction might be the mechanisms of cardiovascular diseases induced by fine particles. Thus,environmental factors such as the fine particles have greatly injured on the endothelial function and it is vital to the occurrence and development of cardiovascular disease,however,statin can improve the function of vascular endothelial cells and protect cardiovasculardiseases,meanwhile,this study verified the pharmacologic action of statin in cardiovascular system.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2010年第1期57-61,共5页
Journal of Clinical Cardiology