内源性一氧化氮在内毒素引起的肺动脉高压和肺损伤中的作用

EFFECTS OF ENDOGENOUS NITRIC OXIDE ON PULMONARY ARTERY HYPERTENSION AND LUNG INJURY INDUCED BY ENDOTOXIN

本实验观察了家兔静脉内注入内毒素的主要成分脂多糖（ＬＰＳ）后平均动脉血压（ＭＡＰ）、肺动脉压（ＰＡＰ）及入、出肺血ＮＯ含量的变化，并观察了静脉内预注入ＮＯ生成抑制剂Ｎω硝基Ｌ精氨酸（ＬＮＮＡ）及诱生型ＮＯ生成抑制剂氨基胍（ＡＧ）后ＰＡＰ和肺损伤的变化。结果观察到：家兔ＬＰＳ注入后，ＭＡＰ均明显下降，ＬＰＳ注入后０５、１、１５、２ｈＰＡＰ明显增高（Ｐ＜００５）。ＬＰＳ注入后ＰＡＰ的高峰期（１ｈ）入肺血ＮＯ含量明显降低，出肺血ＮＯ无明显变化。与对照组相比，ＬＰＳ注入后３ｈ出肺血ＮＯ含量和５ｈ入、出肺血ＮＯ含量均明显增多。相关分析表明，兔ＬＰＳ注入前和ＬＰＳ注入后１ｈＰＡＰ与入肺血ＮＯ含量呈明显的负相关，而ＬＰＳ注入后３ｈ和５ｈ两者相关不明显。静脉预注入ＬＮＮＡ后，ＬＰＳ处理组的动物ＰＡＰ明显增高，入、出肺血丙二醛（ＭＤＡ）含量也明显增高，动物生存率明显降低。肺组织光镜下可见肺萎陷和小血管淤血加重，白细胞明显增加。静脉预注入ＡＧ后，ＬＰＳ处理组的动物ＭＡＰ在３～５ｈ明显增高，此时ＰＡＰ无明显改变，但５ｈ时血中ＭＤＡ含量明显减低，５ｈ时与ＬＰＳ组相比肺萎陷和小血管淤血减轻，白细胞也明显减少。以上结果?

Changes in mean artery pressure(MAP), pulmonary artery pressure(PAP) and nitric oxide(NO) contents in inflow and outflow pulmonary blood(IPB, OPB) were observed after endotoxin lipopolysacchride (LPS) was injected iv in rabbits.Changes of PAP and lung injury were also observed after inhibitor of NO synthesis L NNA or inhibitor of inducible NO synthesis AG was pre injected by vein.The results showed that MAP decreased significantly after LPS administration, and 0 5 ～2 h later PAP showed some increase( P < 0 05 ) being maximum at PAP (1 h) during which the content of NO in IPB was detectably decreased but NO in OPB did not.NO contents in OPB at 3 h and in IPB and OPB at 5 h increased significantly following LPS administration as compared with control.PAP correlated negatively with NO in IPB at the time before and 1 h after LPS injection, which did not exist at 3 and 5 h after LPS injection. After L NNA pretreatment, when PAP elevated significantly, the MDA content in IPB and OPB also showed significant increase, while animal survival rate fell significantly. Light microscopic examination showed severe alveolar atelectasis, significant congestion and sequestration of leukocytes in lung tissue. When pretreated with AG, MAP elevated significantly in 3～5 h, PAP remained unchanged. The MDA content in blood was lower at 5 h in the LPS injected group with less pathological changes in lung tissue at 5 h compared with the LPS group. The above results suggested that there was pulmonary hypertension in the early stage after endotoxin administration.The decrease of NO content in IPB may be one of the mechanisms underlying pulmonary artery hypertension(PAH).NO seemed to alleviate PAH and lung injury at the early stage after endotoxin administration. When iNOS was induced at the later stage, NO contributed to lung injury caused by endotoxin.