Study Of Pulmonary Surfactant In Rats With Endotoxin-induced Acute Lung Injury

Objective Pulmonary surfactant(PS) deficiency is the main cause of neonatal respiratory distress syndrome (NRDS), and surfactant-replacement therapy has achieved great success. Whether the alteration of PS is the main cause of acute lung injury(ALI)/ acute respiratory distress syndrome (ARDS) has not understood clearly. In our experiment, the aim is to study the alterative trend of PS in rats with endotoxin-induced acute lung injury. Methods Fifty-six adult Wistar rats were randomly divided into normal saline (NS) group and ALI group. An equal number of animals in each group were sacrificed after sublingual venous injection of NS or LPS at 1hr, 3hr, 5hr, and 7hr. The levels of mRNA of the surfactant-associated protein-A,-B(SP-A,-B)were measured by reverse transcription polymerase chain reaction (RT-PCR). The content and component of PS in the bromchoalveolar lavage fluid (BALF) were measured by high performance liquid chromatography (HPLC). In addition, lung dry/wet weight ratio, the protein content of BALF, alveolar oxygen partial pressure (PaO2) and histological changes were performed.Results Compared to NS group, in ALI group were observed that the serious intoxical symptom: activity decreace, tachypnoea, and lower PaO2. The histological changes in ALI group show that diffuse alveolar damage, inflammatory cells were found increasingly in capillaries, interstitial tissue, airspaces. Interstitial edema and alveolar haemorrhagia can be found. Lung dry/wet weight ratio at 1,3,5,7hr were lower than the NS group(P<0.05). the content of BALF protein at 1,3,5,7hr were higher than the NS group(P<0.05), PaO2 at 3,5,7hr were lower than NS group(P<0.05). TPL of BALF at 1,3,5,7hr were lower than the NS group(P<0.05), phosphatidylcholine(PC) at 3,5,7hr were lower than the NS group(P<0.05) and decreasedprogressively. Lysophosphatidylcholine (LPC) at 1,3,5,7hr were higher than the NS group(P<0.05) , and increased progressively. the expression contents of SP-A, SP-B, mRNA at 3,5,7hr were less than the NS group(P<0.05), and decreased progressively.Conclusion 1. After injection of LPS, the rats were observed that the tachypnoea, and the blood gas show that decreased PaO2 remarkedly, the histological changes show that interstitial oedema and alveolar haemorrhagia which were coincided with human ALI clinical criteria. The current research successfully established a rat model of LPS-induced acute lung injury(ALI).2. The changed metabolism of PS exists in the pathogenesis of ALI, which mainly shows that the decreased TPL,PC , increased LPC and the decreased expression of SP-A, SP-B mRNA .3. The decreased content and changed components of PS maybe play an important role in a further decrease in pulmonary compliance, lead to the alveoli collapse, atelectasis and severe hypoxemia in ALI.4. PS replacement therapy may be an effective method for ALI/ARDS.