NO调控剂(S,S)-ZX-5及其对映体对血管内皮细胞NO释放及eNOS酶活性影响研究

目的:考察(S,S)-ZX-5及其对映体对血管内皮细胞一氧化氮(NO)释放和内皮型一氧化氮合酶(eNOS)活性的影响,为开发通过增加NO释放而选择性改善脉络膜血流的药物提供理论依据。方法:采用细胞培养技术和硝酸还原酶法在体外测定NO的释放量,用同位素方法测定[H3]L-Arg催化生成[H3]L-Cit量的变化来反映eNOS活性。结果:(S,S)-ZX-5使NO生成显著增加,并与(S,S)-ZX-5的浓度相关,(R,R)-ZX-5对NO生成增加影响不显著;(S,S)-ZX-5显著提高了eNOS酶活性,(R,R)-ZX-5对eNOS酶活性影响不显著。结论:(S,S)-ZX-5改善脉络膜血流的机制可能是通过增强eNOS酶活性,促进细胞内NO释放增加而完成的。

Effect of (S,S)-ZX-5 and its enantiomer on NO production and eNOS activity in ECV304 cells

Aim:To investigate the effect of(S,S)-ZX-5 and its enantiomer on nitric oxide(NO) production and eNOS activity in ECV304 cells,so as to develope a new drug which can specifically improve choroid blood flow by increasing the release of NO.Methods:Cell culture was used for in vitro experiments to determine production of NO by a nitrate/nitrite colorimetric assay kit.eNOS activity was measured by conversion of L-Arg to[H~(3)]L-Cit.Results:It was found that(S,S)-ZX-5 significantly increased the release of NO and eNOS activity,while(R,R)-ZX-5 was not effective on NO release or eNOS activity.Conclusion:Effect of(S,S)(ZX-5) on NO production and eNOS activity could specifically facilitate choroid blood flow.