文本框: Oxidative Stress, Surfactant and Its Effects on Hemodynamics Ola Didrik Saugstad Department of Pediatric Research, The National Hospital, University of Oslo, Oslo, Norway The respiratory tract lining fluid is high in antioxidants . This is the first line in protection versus high oxygen concentration in the airways. Surfactant which forms a thin film in the air-water interface on the alveoli may have an important role in lung defence. The epithelial lining fluid in the centroacinar region of the lung has a lower antioxidant level than the fluid lining the airways higher up. Surfactant may, however, be oxidized and hence inactivated because it is fragile and less surface active. Lipid peroxidation has been demonstrated by exposure to plamsa from premature infants by contrast to plasma from adults. The reason might be that plasma from the former contains free iron which is normally not found in adult plasma. Surfactant proteins are also target for free radicals and can be denaturated by oxygen radicals as well as NO. Activated alveolar macrophages secrete both nitric oxide and superoxide into the alveolar lining fluid, and peroxynitrite inhibits pulmonary surfactant function by lipid peroxidation and damage of surfactant proteins. The first step in oxidant attack is penetration of the broncho-alveolar epithelial lining fluid. Oxidised SP-A has lost is surface active and immune defence functions. The next step is a direct damaging effect on the epithelial and endothelial cells. Due to inflammation and edema transudated plasma proteins and inflammatory cells impair extracelllular surfactant. Superoxide, hydroperoxide and NO may be produced and consequently the toxic peroxynitrite radical. Rabbits exposed to 100% oxygen for 64 hr have a decline in the surfactant phospholipids. The enzyme glycerol-3 phosphate acyltransferase, the enzyme that catalyses the first reaction in phosphoglyceride synthesis, is a rate regulatory enzyme that is extremely sensitive to oxidative damage. Further, hyperoxia results in increase in protein level in bronchoalveolar lavage fluid, and rats exposed to 85% oxygen progressively increased the amounts of surfactant proteins SP-A, SP-B, and SP-C in alveolar lavage fluid. This increase in surfactant proteins was associated with increased relative abundance of mRNA encoding each of the proteins in lung tissue. Type II cells exposed to reactive oxygen species demonstrated a decrease in phosphatidylcholine synthesis with only minimal changes in cell viability. The activities of choline phosphate cytidyltranferase and choline phosphotransferase, which are specific enzymes in phosphatidylcholine synthesis, did not decrease during exposure. In adult rabbits exposed to 100% oxygen for 64 hr a decreased clearance of instilled surfactant from the alveolar space probably due to hyperoxic dysfunction of type II pneumocytes was found.