丙丁酚对自由基损伤内皮细胞的保护作用与一氧化氮的关系

Correlation between the Protection of Probucol on Injury of Endothelial Cells by Free Radicals and the Activity of Nitric Oxide

本文观察了抗氧化剂丙丁酚对外源性氧自由基损伤动脉内皮细胞的保护作用与其对一氧化氨合成释放的关系．结果显示：兔胸主动脉血管环和培养牛主动脉内皮细胞与黄嘌呤＋黄嘌呤氧化酶孵育３０ｍｉｎ后，乙酰胆碱诱导的血管舒张百分率减少，内皮细胞释放一氧化氮的能力降低，脂质过氧化物含量升高。丙丁酚（４０、８０和１２０μｍｏｌ·Ｌ（－１））均能保护内皮细胞免受黄嘌呤＋黄嘌呤氧化酶损伤，且呈剂量依赖性。丙丁酚的作用可被一氧化氮灭活剂氧化血红蛋白阻断而不能被一氧化氮合成酶抑制剂Ｎ－硝基－Ｌ－精氨酸阻断。血管内皮一氧化氮合成与效应抑制实验显示：Ｎ－硝基－Ｌ－精氨酸、氧化血红蛋白和一氧化氮效应拮抗剂美蓝均能使乙酰胆碱诱导的血管环舒张百分率降低。丙丁酚能对抗氧化血红蛋白和美蓝的作用，但对Ｎ－硝基－Ｌ－精氨酸的作用无影响。表明丙丁酚保护血管内皮细胞免受氧自由基损伤可能与保护内皮细胞释放的一氧化氮活性有关。

We investigated the effects of probucol on endothelial damage induced by exogenous free radicals and on activity of nitric oxide (NO).The results demonstrated that rabbit aortic rings incubated with xanthine(X,100 μmolL-1) and xanthine oxidase(XO,100 U·L-1) for 30min showed weak response to acetylcholine and that cultured bovine aortic endothelial cells incubated with X-XO for 30 min showed decrease of NO release and increase of malondialdehyde content.Probucol (40, 80 and 120 μmol·L-1) could protect endothelial cells from injury due to X-XO in a concentration-dependent menner, Inactivator of NO oxidized hemoglobin(OHb, 100μmol·L-1), not synthesis inhibitor of NO NG-nitro-L-arginie(NG-L-Arg,100 μmol·L-1), could abolish the effect of probucol. In the inhibitive experiment of NO synthesis and effect, we observed that the acetylcholine -induced relaxation ratio of aortic rings was reduced by NG-L-Arg, OHb and NO antagonist methylene blue(MB,100 μmol·L-1).Probucol 80 μmol·L-1 could contend with the relaxing inhibition of O Hb and MB not NG-L-Arg. Our data indicate that probucol can protect endothelial cells from damage due to free radicals. The mechanism of such protection may be partly associated with the maintenance of NO activity.