肺动脉高压大鼠一氧化氮及过氧化氢依赖的可溶性鸟苷酸环化酶通路的变化  

Changes of NO- and H_2O_2-dependent soluble guanylate cyclase pathway in the hypoxic hypercapnic pulmonary hypertension rats

作　　者：夏晓东[1] 杨雷[2] 徐正衸[3] 戴元荣[1] 吴淑珍[2] 张洪勤[2] 

机构地区：[1]温州医学院附属第二医院呼吸内科,浙江温州325027 [2]温州医学院分子生物学中心,浙江温州325027 [3]温州医学院病理生理教研室,浙江温州325027

出　　处：《中国病理生理杂志》2006年第4期726-729,共4页Chinese Journal of Pathophysiology

基　　金：浙江省自然科学基金资助项目(No.396479)

摘　　要：目的:观察低O2高CO2对血浆一氧化氮(NO)、肺组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、可溶性鸟苷酸环化酶(sGC)活性以及cGMP含量的变化,探讨NO-sGC和H2O2-sGC通路于肺动脉高压中的作用。方法:复制低O2高CO21、2、4周组及对照组大鼠模型。测定平均肺动脉压(mPAP)。比色法测定血浆一氧化氮(NO)、肺组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性,酶动力学分析基础及过氧化氢(H2O2)及硝普钠(SNP)激活的肺组织sGC酶活性,[125I]-放射免疫法检测肺组织cGMP含量。结果:低O2高CO21、2、4周组mPAP均明显高于对照组(均P<0·01);血浆NO、肺组织SOD、CAT活性、基础sGC活性、过氧化氢(H2O2)及硝普钠(SNP)激活的sGC活性和肺组织cGMP含量均显著低于对照组(分别P<0·05,P<0·01)。结论:低O2高CO2抑制NO-sGC和H2O2-sGC通路参与肺动脉高压的形成与发展。AIM： To study, the effect of hypoxia and hypercapina on nitric oxide （NO） in plasma and superoxide dismutase （SOD）, catalase （CAT）, soluble guanylate cyclase （sGC）, cyclic guanosine monophospholate （cGMP） in lung tissue in rats, and to explore the effect of NO- and H2O2 - sGC pathway on the development of the pulmonary hypertension. METHODS： The model of hypoxie and hypercapnic 1, 2, 4- week group （HH 1 week, HH 2 weeks, HH 4 weeks） and control group was set up. NO content in plasma, CAT and SOD in rat lung were determined by spectrophotometry. The sGC activity in lung tissue was detected by enzyme kinetic analysis. cGMP content in lung tissue was examined with [^125I] -radioimmunoassay. RESULTS： The mean pulmonary artery pressure （mPAP） showed significantly higher in HH 1 week, HH 2 weeks and HH 4 weeks groups compared with control group （all P 〈 0.05）. NO concentration in plasma, CAT, SOD, basal or nitroprusside- or H2O2 - stimulated sGC activity and cGMP concentration in lung homogenates were significantly lower （ P 〈0.05, P 〈0.01, P 〈0.01, respectively） in HH 1 week, HH 2 weeks and HH 4 weeks groups compared with control group. CONCLUSION： The inhibition of NO- and H2O2 - sGC pathway by hypoxia and hypercapnia plays an important role in the development of pulmonary hypertension.

关 键 词：缺氧 高碳酸血症 肺动脉高压 鸟苷酸环化酶 自由基 一餐化氮 信号转导 

分 类 号：R363[医药卫生—病理学]