The Mechanisms Of No And ET In Acute Lung Injury PUP RAT Model

Objective: Recently investigations display nitric oxide(NO)and endothelin(ET) play an important role in pathophysiology of acute lung injury(ALI). infants are prone to develop actue lung injury(ALI). However, little information was available on the potential effect of Nitric oxide(NO)and endothelin(ET) in mediating ALI . This study aimed to investigate the change of NO﹑nitric oxide synthase(NOS)and ET as well as the expression of NOS in the lung by using LPS－induced lung injury.Methods:Fiftysix healthy pup rat (clean animal ,CL) was randomly classified normal saline (NS) group and ALI group. we examined the concentration of NO﹑ET and NOS activity by way of chromatometry and Radio-immunoassay (RIA) during iv injection of endotoxin after 1﹑3﹑7hours.The mRNA levels of NOS were measured by reverse-transcription polymerase chain reaction(RT-PCR). In addition, lung dry/wet weight ratio, the protein content of bronchoalveolar lavage fluid (BALF), femoral arterypartial pressure of oxygen(PaO2), histologicalchanges were performed. Results: Compared to NS group, ALI group developed severe lung damage. The histological changes consisting of interstitial edema, haemorrhage and inflammatory were found. There were a significant increase in protein content(mg/ml) in BALF during ALI 1h(0.25±0.03)﹑3h(0.34±0.03)﹑7h(0.40±0.07)VS NS(0.20±0.09,P<0.05), and the lung dry / wet weight ratio was significantly decreased ALI 1h(0.20±0.09)﹑3h(0.18±0.07)﹑7h(0.17±0.06)VS NS(0.22±0.02,P<0.05).artery partial pressure of oxygen decreased significantly at the same time. At ALI 7 hours the artery partial pressure of oxygen is reached(7.27±0.42)kpa. At ALI group the concentration of NO(μg/ml) 1h(64.46±11.69)﹑3h(101.40±21.32)﹑7h(120.30±16.67) VS NS(44.43±6.33,P<0.05)and ET(pg/ml)ALI 1h(517.96±33.21)﹑3h(101.40±21.32)﹑7h(120.30±16.67) VS NS(44.43±6.33,P<0.01)both significantly increased, meanwhile NOS activity(u/mgpro) ALI1h(0.30±0.05)﹑3h(0.34±0.03)﹑7h(0.45±0.09) VS NS(0.24±0.03,P<0.05)significantly increased. NO ﹑ET both increased but ET/NO ratio more significantly during early stage ALI.iNOS mRNA expression in the ALI group1h(0.70±0.20)﹑3h(1.88±0.31)﹑7h(2.64±0.38) VS NS(0)were significantly elevated(P<0.01). The eNOS mRNA expression was not statistically significant(P＞0.05). Conclusions: 1. After injection LPS animal characterized by hypoxia, dyspnea,comprehensive inflammatory infiltraton and interstitial edema in lung , damage of alveolar formation and lung edema.2. In ALI progress, NO and ET of concentration was significantly increased. that show NO and ET participated in pathophysiology process of lung injury.3. Overexpression of NO associated with increased activity of NOS, which resulted mainly from high expression of iNOS mRNA.4. Early time elevated ET in ALI may be the stimulator lead to the production of NO, contimuously and greatly.