血管组织肾素—血管紧张素系统激活对活性氧及一氧化氮生成的影响
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湖南省重点科技项目(OISSY1003)


The Effects of Activation of the Vascular Tissue Renin Angiotensin System on Production of Reactive Oxygen Species and Nitric Oxide
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    目的研究血管组织肾素—血管紧张素系统激活对活性氧及一氧化氮生成的影响。方法采用五指山小型猪10头,分为2组,每组5头,分别喂饲正常或高脂饮食3个月,观察颈总动脉组织胆固醇含量、血管紧张素Ⅱ、活性氧、一氧化氮及总抗氧化能力的变化,并应用chymostatin和氯沙坦分别抑制培养的人脐静脉内皮细胞血管紧张素Ⅱ生成或阻断其与受体结合,测定细胞培养液中活性氧和一氧化氮含量。结果高脂血症猪血管组织内膜与中膜胆固醇含量较对照组增加了108%±25%,血管紧张素Ⅱ含量增加了115%±20%,活性氧含量增加了144%±28%,一氧化氮减少了51%±5%,血管组织总抗氧化能力降低56%±5%(P均<0.01)。人脐静脉内皮细胞培养液中加入血管紧张素Ⅰ10 nmol/L,培养液中血管紧张素Ⅱ增加11倍,活性氧生成显著增加,一氧化氮则显著减少(P均<0.01)。人脐静脉内皮细胞培养液中加入血管紧张素Ⅰ10 nmol/L和Chymostatin 100或500μmol/L,血管紧张素Ⅱ的生成分别降低了61%±6%和65%±7%,同时活性氧生成减少,一氧化氮生成增加(p<0.01);人脐静脉内皮细胞培养液中加入氯沙坦,在血管紧张素Ⅱ生成不减少的情况下,活性氧与一氧化氮生成量与对照组相近。结论高胆固醇血症能使猪血管组织肾素—血管紧张素系统活化,导致活性氧生成增多,一氧化氮减少,这一作用可能由血管紧张素Ⅱ的I型受体介导。

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    Aim To investigate the effects of activated renin angiotensin system in the vascular tissue on production of reactive oxygen species and nitric oxide.Methods Ten male Wuzhishan minipigs were divided into two groups,fed with normocholesterolemic(control;n=5) or hypercholesterolemic(2% cholesterol,hyperlipid,n=5) food for 3 months.Carotid arteries were isolated and the changes of TC,AngⅡ,ROS,NO and T-AOC of the vascular tissue were determined.In addition,hUVEC(human umbilical vein endothelial cell) were incubated with Ang I and chymostatin or with Ang I and losartan respectively for 24 h,the suspernatant was collected to measure the concentration of AngⅡ,ROS and NO. Results In comparison to the normocholesterolemic state,hypercholesterolemia led to a significant increase in TC content(108%±28%,p<0.01),AngⅡ generation (115%±20%,p<0.01) and ROS production(144%±28%,p<0.01),but it led to a significant decrease in NO(51%±5%,p<0.01) and T-AOC(56%±5%,p<0.01).Cultrured hUVEC could convert Ang I to AngⅡ.AngⅡ increased by11 times in the presence of 10 nmol/L Ang I as compared with control group,and the level of ROS also increased while NO decreased significantly.When hUVEC were incubated with Ang I plus 100 or 500 μmol/L chymostatin,AngⅡ generation was reduced by 61%±6% or 65%±7% respectively,and the ROS decreased while NO increased significantly as compared with only Ang I.When hUVEC were incubated with Ang I plus Losartan,the generation of ROS and No was almost the same as compared with control group on condition that AngⅡ generation was not reduced. Conclusion hypercholesterolemia could activate renin angiotensin system of the vascular tissue,which results in an increased vascular tissue production of ROS and a decreased NO.This effect might be mediated by AT1 receptor.

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孙文清,冯大明,唐朝克,刘录山,王仁,万载阳,杨永宗.血管组织肾素—血管紧张素系统激活对活性氧及一氧化氮生成的影响[J].中国动脉硬化杂志,2006,14(1):29~31.

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  • 收稿日期:2005-04-29
  • 最后修改日期:2006-01-23
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