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微血管病性心绞痛患者血小板L-精氨酸-一氧化氮系统改变及静脉L-精氨酸输入的逆转效应
田海涛1,高连如2*,张宁坤2,王志国2,陈宇2,朱智明2,费宇行2,杨晔2,唐朝枢3
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(1.海军总医院干一科,北京 100037*2.海军总医院心内科,北京 100037*3.北京大学第一临床医院,北京 100034)
摘要:
目的:观察微血管病性心绞痛(MVA)患者血小板左旋精氨酸(L-Arg)转运动力学、一氧化氮合酶(NOS)活性及一氧化氮(NO)产量,探讨血小板L-Arg-NO系统变化在MVA发病中的意义,及静脉输入L-Arg对L-Arg转运的逆转效应。方法:15例MVA患者及15例健康对照者,静脉血制备血小板悬液,用放射性核素标记法测定3H-L-Arg 在血小板的转运动力学特征; 测定血小板NOS活性及NO产物——亚硝酸盐(NO-2)量; 15例MVA患者基础检查后,给予静脉滴入L-Arg 20 g/d,10 d后重复上述检查。结果:MVA患者血小板L-Arg转运功能明显减低,最大转运速率(Vmax)较对照组减低34.4% (P<0.01); L-Arg转运米氏常数(Km)值增加21.4%(P<0.05); NO-2产量较对照组减少47.1%(P<0.05),NOS活性较对照组减低25.4%(P<0.01)。而应用L-Arg可明显逆转上述改变,与MVA组治疗前比较Vmax增加11.9% (P<0.01),Km降低18% (P<0.05),NO-2产量明显增加,是治疗前的1.33倍(P<0.05),NOS活性增加为治疗前的1.2倍(P<0.05)。L-Arg静滴后心绞痛发作及心电图明显改善。结论:MVA患者存在L-Arg-NO系统转运及功能障碍,MVA患者冠脉微血管内皮依赖性舒张功能障碍可能与L-Arg-NO系统障碍有关。L-Arg的补充可逆转L-Arg-NO系统障碍,在MVA治疗上有重要作用。
关键词:  微血管病性心绞痛  L-Arg-NO转运系统  一氧化氮合酶  L-精氨酸
DOI:10.3724/SP.J.1008.2009.00040
投稿时间:2008-04-30修订日期:2008-11-20
基金项目:
Changes of L-arginine-NO pathway in platelets of microvascular angina patients and reversing effects of intravenous L-arginine infusion on L-Arg-NO transport
TIAN Hai-tao1,GAO Lian-ru2*,ZHANG Ning-kun2,WANG Zhi-guo2,CHEN Yu2,ZHU Zhi-ming2,FEI Yu-xing2,YANG Ye2,TANG Chao-shu3
(1.No.1 Department of Cadres,Navy General Hospital of PLA,Beijing 100037,China*2.Department of Cardiology,Navy General Hospital of PLA,Beijing 100037*3.The First Clinical Hospital,Beijing University,Beijing 100034)
Abstract:
Objective:To observe the L-Arg(L-arginine) transport,the nitric oxide (NO) production,and NO synthase (NOS) activity in platelets,investigate the significance of the L-Arg-NO system in the pathogenesis of microvascular angina(MVA),and to study the reversing effects of intravenous L-Arg infusion on L-Arg transport.Methods:The 3H-L-Arg transport,NO production,and NOS activity in platelets were examined in 15 patients with MVA and 15 healthy controls.The 15 patients were given intravenous L-Arg infusion (20 g/d) after basic physical examination and were examined again 10 days later.Results:The L-Arg transport in platelets of MVA patients was obviously lower than that in the normal group; the maximum transport velocity (Vmax) decreased by 34.4% compared with the normal group (P<0.01); and the Michaelis constant (Km) increased by 21.4% (P<0.05).The production of NO-2 and the activity of NOS in platelets were decreased by 47.1% (P<0.05) and 25.4% (P<0.05) compared with the normal group,respectively.Intravenous L-Arg infusion reversed the above changes in MVA patients; it increased the Vmax by 11.9% (P<0.01) and decreased Km by 18% (P<0.05); it also increased production of NO-2 by 1.33 folds (P<0.05) and NOS activity by 1.2 folds (P<0.05).Especially,the attack of angina and patient ECG were greatly improved after intravenous L-Arg infusion.Conclusion:L-Arg-NO pathway is impaired in MVA patients,which might be responsible for the endothelium-dependent vascular relaxation in MVA patients.Intravenous L-Arg infusion may benefit the impaired function of L-Arg-NO transport in patients with MVA.
Key words:  microvascular angina  L-Arg-NO pathway  nitric oxide synthase  L-arginine