摘要
目的前期研究表明ZX-5中的一个异构体(R,R)ZX-5,能够促进脉络膜血流和增加NO的释放量。该研究是为了进一步阐明ZX-5是通过上调哪种一氧化氮合酶(NOS)的表达或活性而达到增加NO释放和促进脉络膜血流的作用。方法 Western blot和一氧化氮合酶活性检测试剂盒测定不同一氧化氮合酶表达和酶活性。结果 (S,S)ZX-5能够上调诱导型一氧化氮合酶(iNOS)表达,而不影响内皮型一氧化氮合酶(eNOS)和神经型一氧化氮合酶(nNOS)表达;而(R,R)ZX-5能够上调eNOS表达,并且iNOS表达也有轻微上调作用,但是不改变nNOS的表达;酶活性测定研究发现(S,S)ZX-5仅仅能通过激活iNOS酶活而增加NO释放量;而(R,R)ZX-5也仅仅能够通过激活eNOS的酶活而增加NO释放。结论和(S,S)ZX-5相比,(R,R)ZX-5能够通过上调eNOS表达和活力,增加NO的释放,进而增加脉络膜的血流;因此(R,R)ZX-5也更加适合开发为治疗年龄相关性黄斑变性的药物。
Aim To investigate effects of ZX-5 on the expression and activity of nitric oxide synthase （ NOS） in endothelial cells,and to confirm which kind of NOS increases NO production and promote choroidal blood flow in ZX-5 -induced HUVECs. Methods HUVECs （ human umbilical vein endothelial cells） were used to determine the expression of eNOS,iNOS and nNOS by Western blot; the activities of NOS were investigated by the corresponding kit. Results （ R,R） ZX-5 upregulated eNOS expression and increased NO production; （ S,S） ZX-5 upregulated iNOS expression and slightly increased NO release. Conclusions （ R,R） ZX-5 promotes choroidal blood flow via upregulating eNOS expression and activity and promoting NO production; the compound may be used for the prevention and treatment of age-related macular degeneration in the elderly.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第8期1029-1033,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30873073)
