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

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、2h PAP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1h PAP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.以上结果提示,内毒素入血后较早期阶段可出现PAP的升高,此时入肺血NO的减少是参与肺动脉压增高(PAH)的机制之一.家兔内毒素进入血后较早期阶段NO对减轻内毒素引起的PAH和肺损伤起重要作用,而较晚的时期当诱生型NO合酶(iNOS)诱生后释放的NO则参与内毒素引起的肺组织炎症反应和肺损伤.

Effects of endogenous nitric oxide on pulmonary artery hypertension and lung injury induced by endotoxin

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 i.v. 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 0.5-2h later PAP showed some increase (P<0.05) being maximum at PAP (1h) during which the content of NO in IPB was detectably decreased but NO in OPB did not. NO contents in OPB at 3h and in IPB and OPB at 5h increased significantly following LPS administration as compared with control.PAP correlated negatively with NO in IPB at the time before and 1h after LPS injection, which did not exist at 3 and 5h 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 3-5h, PAP remained unchanged. The MDA content in blood was lower at 5h in the LPS injected group with less pathological changes in lung tissue at 5h 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.