更换他汀类药物对内皮细胞NO合成的影响

Effects of switching statins on nitric oxide production in vascular endothelial cells in vitro

关键词:  辛伐他汀  洛伐他汀  一氧化氮  一氧化氮合酶

Key words:  simvastatin  lovastatin  nitric oxide  nitric oxide synthase

摘要:

目的 观察更换他汀类药物对人脐静脉内皮细胞（Human umbilical vein endothelial cells,HUVECs）一氧化氮（Nitric Oxide,NO）合成的影响。方法 将HUVECs暴露于辛伐他汀(10^-6mmol/L)孵育24h,洗涤后换用同浓度的洛伐他汀,继续加入同浓度的原药继续培养24h,分别用Griess试剂测定培养液中NO的产量,并用逆转录聚合酶链式反应（Reverse transcription polymerase chain reaction,RT-PCR）方法测定换用他汀类药物24h对HUVECs内皮型一氧化氮合酶（endothelial nitric oxide synthase,eNOS）mRNA表达的影响。结果 应用辛伐他汀24h,NO产量较对照组增加了（103±31）%,（P＜0.05）。而换用洛伐他汀后,NO的产量较继续应用辛伐他汀减少了68%±7%（P＜0.05）,与对照组相比没有显著统计学差异。辛伐他汀换用洛伐他汀后较继续应用辛伐他汀eNOSmRNA表达减少了（53±11）%,（P＜0.05）。结论 更换他汀类药物可在短期内显著减少NO的合成和eNOS的表达,可能是导致心血管事件增加的原因之一。

Abstract:

Objective To investigate the effects of switching statins on nitric oxide（N）)production in human umbilical vein endothelial cells（HUVECs）.Methods HUVECs were exposed to simvastatin(10^-6mmol/L)for 24 h;after wash,HUVECs were exposed to lovastatin with same concentration,or continued to be exposed to simvastatin for another 24 h.The NO production was measured by Griess reagent;and levels of endothelial nitric oxide synthase（eNOS）mRNA were examined by RT-PCR.Results Compared to the control levels,continuing simvastatin exposure increased the NO production in HUVECs by（103±31）%（P＜0.05）.Compared to continuing simvastatin exposure,switching to lovastatin reduced the NO production by（68±7）%（P＜0.05）, and there was no significant statistical difference to control levels.When simvastatin was switched to lovastatin the expression of eNOS mRNA in HUVECs was decreased by（53±11）%（P＜0.05） compared to continuing simvastatin exposure.Conclusion Switching statins can decrease the production of nitric oxide and the expression of eNOS mRNA in HUVECc,which may account for high cardiovascular events when statins are switched in clinical study.