The Research On The Mechanism Of Neonatal Rats Pulmonary Hemorrhage Caused By Lipopolysaccharide

Pulmonary hemorrhage of newborn ( PHN ) is one of fatal disease commonly seen in neonatal intensive care unit, which is difficult to diagnose in the early phase. The morbidity of PHN is not declined in prematures since the application of pulmonary surfactant and the mortality is 40 - 50%. There are many predisposing factors caused PHN including asphaxia, infection, PDA, cold injury, prematures, the abnormal coagulation et al. The pathogenesis of PHN is not known clearly yet. The results of clinical research showed us that the elastic fiber in the alveolar barrier and the basement in the capillary are disrupted in PHN. The contract function of left ventricle is decreased in the neonates died from PHN contrasted with the living person with PHN. PHN is more easily seen in prematures, very low birth weight infants and IUGR infants now. It is reported that PHN in prematures is correlated with PDA and the higher lung blood volume. The basic research on pulmonary hemorrhage (PH) recently showed us that the stress failure of the pulmonary capillary is one of reasons of PH which is happened in the persons with the deficient collagen IV in the basement membrane in pulmonary capillary. It will be resulted in the lung edema and disseminated PH. The pathologic change of the stress failure includes the disruption of endothelial cells, epithelial cells and the basement membrane which is the same as that of PHN. It is obvious that the lung vessel is more premature in prema-tures than that of normal newborns, which is the same comparing the newborns with the adults. The difference of the development of lung vasculature is one of predisposing factors of higher morbidity of PH in neonates, especially in prematures. But it is important to identify that the injury of pulmonary capillary is existed in PHN. It is the injury of pulmonary capillary endothelial cell and the basement membrane that caused the newborns with premature lung tissue occur PH easily under some causes.The classical animal model of the adult ARDS is caused by LPS. Infection is the common cause of PHN. But there is no animal model of PHN. We prepared pulmonary hemorrhage animal model with the neonate rats by LPS injected intraperitoneally in order to explain the mechanism of the change of lung tissue of neonate rats comparing with the change of adult rats. It is known that the pulmonary capillary is injured in the patients of adult ARDS. And the disruption of pulmonary capillary 'basement membrane is found in the neonate died from PH.Those data revealed that pulmonary capillary basement membrane plays an important role in the pathogenesis of PHN. From that, we did the experiment with neonatal rats. The rats was injected intraperitoneally by LPS and their lungs was observed by the microscope and the electron microscope from which the disruption of pulmonary capillary basement membrane can be seen. The main part of the basement membrane is collagen IV and lamina, which will be changed and detected by immunohistochemistry and in situ hybrization. MMP - 2 and TIMP -2 belong to the degradation system of collagen IV and lamina, which will be detected by immunohistochemistry and RT - PCR. One of the main factors that modulate the MMP system is plasmin which is converted from plasminogen by plasminogen activator. And the tissue - plasminogen activator and the plasminogen activator inhibator - 1 and PEC AM - 1 are secreted by endothelial cells, which will be detected by immunohistochemistry and RT - PCR. It will be proved that the function of pulmonary endothelial cells is important in the pathogenesis of PHN. It is the injury and the changes of morphology and function of pulmonary endothelial cells caused by LPS that make the basement membrane disruption and make the lung in hypercoagulation that cause PHN. From the a-bove, we can express the mechanism of PHN caused by LPS and can provide scientific basis for the treatment of PHN.Materials and Methods1. Animal modelThe neonatal Wistar rats(7-days, weight; 12 - 18g) are starved 4h before e...