对内皮细胞产生超氧阴离子作用的研究  

Experimental Study on Superoxide Anion Generation in Endothelial Cells

作　　者：曹路[1] 黄体钢[2] 杨万松[2] 丛洪良[1] 周丽娟[2] 倪燕萍[2] 

机构地区：[1]天津市胸科医院心内科,300051 [2]天津医科大学第二医院心脏内科

出　　处：《中国循环杂志》2009年第2期137-140,共4页Chinese Circulation Journal

摘　　要：目的:研究四氢生物喋呤(BH_4)、L-精氨酸、局部血管紧张素Ⅱ生成对内皮细胞产生超氧阴离子(O_2^-)的作用以探讨它们对内皮功能的影响。方法:将BH_4、L-精氨酸、血管紧张素Ⅰ和厄贝沙坦加入体外培养的人脐静脉内皮细胞(HUVECs),根据不同干预浓度及干预因素组合,实验共分14组,干预8小时后取出上清液分别测定O_2^-(Fenton反应原理)、一氧化氮(NO,硝酸还原酶法)和血管紧张素Ⅱ(放射免疫分析法)的浓度。结果:与对照组相比,不同浓度的BH_4和L-精氨酸组的血管紧张素Ⅱ水平均显著减低,NO水平显著升高(除外L-精氨酸10μM组);BH_420μM组O_2^-水平显著降低,差异均有统计学意义(P<0.05～0.01)。与对照组相比,血管紧张素Ⅰ加不同浓度的BH_4和厄贝沙坦各组NO水平升高,差异均有统计学意义(P<0.05～0.01)。与对照组相比,血管紧张素Ⅰ组O_2^-的产生增加,差异均有统计学意义(P<0.05～0.01);与血管紧张素Ⅰ组相比,血管紧张素Ⅰ加不同浓度的BH_4和厄贝沙坦各组的O_2^-水平均显著降低,差异均有统计学意义(P<0.05～0.01)。结论:BH_4在防止一氧化氮合成酶解耦联中可能起主要作用,BH_4和L-精氨酸均能促进NO的产生并且抑制血管紧张素Ⅱ的生成。BH_4及BH_4和厄贝沙坦合用可以抑制局部血管紧张素Ⅱ生成引起的O_2^-产生增加,并促进NO的产生。Objective ：To explore the impact of terahydrobiopterin （ BH4 ）, L-arginine （L-Arg） and local angiotensin Ⅱ （Ang Ⅱ ） formation on endothelial function by observing their effects on endothelial cells HUVECs superoxide anion（ O2^- ） generation. Methods ：HUVECs were cultured with BH4 , L-Arg,angiotensin Ⅰ （Ang Ⅰ ） and lrbesartan （Irb） for 8 hours, and then the levels of O2^- ,nitric oxide（NO） and Ang Ⅱ in the supernatant of conditioned medium were measured. Results：Different dosage of BH4 and L-Arg suppressed Ang Ⅱ production. Increased levels of NO were induced by BH4 （10 μM, 15 μM,20 μM） and L-Arg（ 100 μM, 1 mM）. When compared with controls, BH4 （20 μM） significantly reduced the level of O2^- However, L-Arg alone had no effect on O2^- generation in HUVECs. Different doses of BH4 diminished the generation of Aug Ⅱ. When compared with controls, BH4 ＋ Ang Ⅰ and BH4 ＋Ang Ⅰ ＋ Irb promoted endothelial NO production. Ang Ⅰ increased O2^- production in HUVECs as compared with control group, and this effect was inhibited by adding BH4 and BH4 ＋ Irb. Conclusions ： BH4 might play a major role in preventing endothelial NO synthase （eNOS） from uncoupling. In addition, both BH4 and L-Arg promoted endothelial NO production and diminished Aug Ⅱ formation. BH4 and BH4 ＋ Irb contributed to suppressing the elevated O2^- induced by local Ang Ⅱ formation and promoting NO production in HUVECs.

关 键 词：超氧阴离子 四氢生物喋呤 L-精氨酸 一氧化氮 血管紧张素Ⅱ 

分 类 号：R54[医药卫生—心血管疾病]