Effects Of Vaporized Perfluorocarbon Therapy On LPS-induced Acute Lung Injury In Surfactant Proteins And Matrix Metalloproteinases

[OBJECTIVE]To investigate the effects of vaporized perfluorocarbon therapy on LPS-induced acutelung injury in animal models and to approach the mechanism of the therapy by testingsurfactant protein and matrix metalloproteinases.[METHODS]Twenty-four famale New Zealand rabbits were ventilated in a volume-controlledmechanical ventilator and randomly divided into four groups:â‘ the ALI+PFC groupreceived conventional mechanical ventilation and vaporized PFC inhalation after acutelung injury was induced by intravenous injection of LPS;â‘¡the ALI group receivedconventional mechanical ventilation after ALI animal models were established;â‘¢the PFCgroup received conventional mechanical ventilation and vaporized PFC inhalation;â‘£theControl group only received conventional mechanical ventilation. The animals in theALI+PFC and ALI groups received vaporized PFC inhalation for2hours followed byconventional ventilation6hours. The venous blood and arterial blood were extracted everyhour during the experiment. The lung was harvested at the end of the experiment andassayed by histopathological techniques and molecular biology techniques.Part1We investigated the effects of vaporized PFC inhalation on respiratorymechanics, hemodynamics mechanics and arterial blood gas indexes during and aftervaporized PFC inhalation therapy. In addition, we observed the structural changes of lung.Part2In order to approach the mechanism of vaporized perfluorocarbon therapy,we evaluated surfactant proteins in plasma, bronchial alveolar lavage fluids(BALF) andlung tissue by ELISA, real-time PCR and Western Blot. In addition, we also measuredErbB1, ErbB4and ErbB1phosphorylation by real-time PCR and Western Blot. Part3To investigate the effects of vaporized PFC inhalation on matrixmetalloproteinases, MMP-2, MMP-9, TIMP-1and TIMP-2in plasma, BALF and lungtissue were evaluated by ELISA and real-time PCR.[RESUILS]1. Vaporized PFC improved the gas exchange, airway resistance and mean arterialblood pressure, and had protective effects on the pathological damage of lung in the ALIanimal models.2. After vaporized PFC inhalation, SP-A, SP-B, SP-C and SP-D in the plasmadecreased, but SP-A, SP-B and SP-C in the BALF increased. Expressions of SP-A, SP-Band SP-C in ALI+PFC group were significantly higher than those in ALI group. Westernblot results showed that vaporized PFC inhalation decrease SP-D level in the ALI+PFCgroup compared to the ALI group, but increased it in the PFC group compared to the Cgroup.3. The mRNA expressions of ErbB1and ErbB4in the ALI+PFC group weresignificantly lower than those in the ALI group. But those mRNA expressiongs in the PFCgroup were statistically higher than in the C group.4. In this study, we found that MMP-2and MMP-9in the plasma, BALF and lungtissue decreased after vaporized PFC inhalation.[CONCLUSION]1. Vaporized PFC inhalation could improve oxygenation indexes and had protectiveeffects on the pathological damage of lung in the ALI animal models.2. Vaporized PFC inhalation enhanced the synthesis and secretion of lung surfactantprotein(SP-A, SP-B and SP-C). It was unknown the effects of vaporized PFC on the SP-D.3. Inhibiting the synthesis and secretion of MMP-2and MMP-9may be one of themechanism of alleviating ALI after vaporized PFC inhalation.