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

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。

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

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 micro-and 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.