内源性硫化氢对高肺血流大鼠肺血管重构及血管活性物质的影响  

Impact of endogenous hydrogen sulfide on pulmonary vascular structural remodeling and vasoactive peptides in rats with high pulmonary blood flow

作　　者：李晓惠[1] 杜军保[1] 唐朝枢[2] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院心血管研究所,北京100034

出　　处：《中国药理学通报》2007年第3期327-331,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30425010;30630031);北京市自然科学基金资助项目(No7052043);国家重点基础研究发展规划资助项目(No2006CB503807)

摘　　要：目的探讨内源性硫化氢(hydrogen sulfide,H2S)对大鼠高肺血流性肺血管结构重建及血管活性肽的影响。方法♂SD大鼠32只随机分为分流组、分流+PPG(炔丙基甘氨酸,内源性H2S合成酶的抑制剂)组、对照组和对照+PPG组,每组8只。经腹主动脉-下腔静脉穿刺建立动物模型。分流4wk后,应用敏感硫电极法测定大鼠肺组织硫化氢(H2S)含量;应用放免试剂盒测定血浆中内皮素(ET-1)、心钠素(ANP)、降钙素基因相关肽(CGRP)及肾上腺髓质素(ADM)的含量;观察肺小血管的显微结构变化;结果分流4wk后,大鼠肺组织H2S水平升高,肺血管结构重建,血浆ET-1、ANP、CGRP及ADM升高。PPG干预后,肺组织H2S水平降低,肺血管结构重建加重,血浆ET-1、ANP、CGRP升高,而ADM降低。结论内源性H2S对高肺血流性肺血管结构重建具有重要的保护作用,并对多种血管活性肽具有调节作用。Aim To explore the impact of endogenous hydrogen sulfide on pulmonary vascular structural remodeling and vasoactive peptides in rats with high pulmonary blood flow. Methods Thirty-two male SD rats, weighing 120～140 g, were randomly divided into shunt group （ n = 8 ）, shunt ＋ PPG （ propargylglycine） group （ n = 8） , control group （ n = 8） and control ＋ PPG （n = 8）. Rats in shunt group and shunt ＋ PPG group were subjected to an abdominal aorta - inferior vena cava shunt to create an animal model of high pulmonary flow. Rats in shunt ＋ PPG group and control ＋ PPG group were intraperitoneally injected with an inhibitor of endogenous H2S generation enzyme-PPG at a dose of 37.5 mg · kg^-1 each day. After 4 weeks of experiment, the morphologic changes including microand ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. H2S concentration in lung tissue was evaluated by sensitive modified sulfide electrode method. Endothelin-1 （ ET-1 ）, atrial natriuretic peptide （ANP）, calcitonin gene related peptide （CGRP） and adrenomedullin （ADM） were calculated by radioimmunoussay kit. Results After 4 weeks of shunt, lung tissue H2S level increased significantly （P 〈 0. 01 ）. Pulmonary vascular structural remodeled. Plasma ET-1, ANP, CGRP and ADM increased significantly （ all P 〈 0. 01 ）. After administration with PPG for 4 weeks to rats with shunt, pulmonary vascular structural remodeling deteriorated. ET-1, ANP and CGRP increased significantly （all P 〈0. 01 ）, whereas ADM decreased significantly （ P 〈 0. 01 ）. Conclusion Endogenous H2S plays an important protective effect on pulmonary vascular structural remodeling in rats with high pulmonary flow, and exerts regulatory effect on many of vasoactive peptides.

关 键 词：硫化氢 肺动脉高压 肺血管结构重建 血管活性肽 

分 类 号：R-332[医药卫生] R322.35