Therapeutic Effects Of Porcine Pulmonary Surfactant On Acute Lung Injury Induced By Oleic Acid In Rats

The acute respiratory distress syndrome(ARDS) describes an overwhelming inflammatory reaction within the pulmonary parenchyma leading to life-threatening disturbances in pulmonary vasomotion, alveolar ventilation, and gas exchange. The early phase of ARDS is termed acute lung injury(ALI). Despite numerous efforts to develop causative or symptomatic treatment options, ARDS still has a high mortality rate of about 50%. Therefore there is a need for alternative therapeutic interventions.In this study, we used a rat model of acute lung injury(ALI) induced by oleic acid. We tried out different doses of oleic acid in order to choose the appropriate one. Through experiments, we found that the dose of 0.20ml/Kg would satisfy our requirements and meet the standard the ALL Then we evaluated the therapeutic effects of porcine pulmonarysurfactant(PPS) on the ALL We estimated survival studies and the respiratory function of lungs with breath rates and arterial blood gases, assessing the lung damage with appearance and pathological structure of lungs. The lung index(LI), the total protein(TP) in the bronchoalveoar lavage fluid(BALF) and TNF-a concentration in plasma were also measured as the sign of degree of lung injury.Firstly, we investigated the therapeutic effects and dose-effect relationship of intratracheal instillation of different doses of PPS (50, 80 , 100, 150, 200mg/Kg) in ALI rats. The results showed that PPS (50mg/Kg) group improved arterial blood gases during the first 2 hours and reduced breath rates. Other PPS-treatment groups not only improved arterial blood gases and reduced breath rates, but also significantly raised 4h-survival rates and decreased lung index, protein contents in BALF and TNF-a concentration in plasma, meliorated histological appearance compared with group given saline after OA. PPS(150, 200mg/Kg) groups provided more efficiently on lung injury than other groups.Secondly, we estimated the therapeutic effects of intratracheal instillating PPS (100, 150mg/Kg) at different time (30min, 2h) on ALI in rats. The experimental method and assessments were the same to mentioned above. The results showed that PPS ( ≥ 100mg/Kg ) administered at the early stage (30min) not only improved respiratory function, but also significantly decreased lung injury. More PPS (≥150mg/Kg) needed at the late stage (2h) had the effects mentioned above. Comparatively the theraputic efficiency of 2h(PPS150mg/Kg) was worse than that of 30min(PPS150mg/Kg), indicated the importance of early administration.The usual way of administering PS is by instilling it as a bolus into the lungs through bronchoscope or endotracheal tube. In this study, we tried another method of inhaling PS driven by oxygen in ALI models. We used a laser aerosol particle counter to measure the size distribution of aerosolized PPS driven by oxygen under various flow rates. The outcome was that if the flow rate was over 2.0 L/min, the particle size distribution of PPS was almost ranging from 0.3um to 2.0um. With raising the flow rate, more PPS particle size was smaller than 1 .Oum. This size of PPS could arrive at the pulmonary alveolus to perform function. Combined with the clinical fraction of inspired oxygen, we decided on the flow rate of 4.5L/min to drive the bolus of PPS into aerosol.Then we evaluated the new method of administering PPS in ALI rats and compared the efficiency of intilling PPS with inhaling PPS. This test showed that two inhaling groups not only improved arterial blood gases and reduced breath rates, but also significantly raised 4h-survival rates and decreased lung index > protein contents in BALF and TNF-a level in plasma, meliorated histological appearance compared with the group given OA. PPS-inhaling group had better effects than saline-inhalinggroup on lung index> protein contents in BALF> TNF-a level in plasma and histological appearance. Inhaling PPS (160mg/Kg) had the same effects with instilling PPS (lOOmg/Kg).From what we studied, we had proved that PPS provided therapeutic effects on animal models of ALI induced by oleic acid. PPS=^80mg/Kg administered at early stage might alleviate the lung injury, however more PPS^150mg/Kg was needed at late stage. Aerosolized PPS (160mg/Kg) also had the therapeutic effects, but the effect was inferior to that obtained with bolus PPS. As this method of inhaling PPS is more convenient and safer, more investigation about the implication of aerosolized PPS is needed.Our findings provide the proofs of efficiency of PPS and help to make up the clinical medication of PS. We also set up a new method of aerosolized PS.