Changes of platelet endothelial cell adhesion molecule-1, tissue type plasminogen activator and plasminogen activator inhibitor-1 expression in the lung tissue of neonatal rats after intraperitoneal injection with lipopolysaccharide
ABSTRACT To further explore the pathogenesis of neonatal acute lung injury and neonatal pulmonary hemorrhage by establishing the animal model of neonatal acute lung injury (ALI) and by investigating the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1), tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in ALI.
Totally 88 neonatal rats which were divided into 8 groups randomly including one normal saline control group and 30 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h post injection groups. The changes of lung pathology in newborn rats were observed at different time after LPS was injected intraperitoneally. The changes of PECAM-1 protein, t-PA and PAI-1 mRNA expression were measured by immunohistochemistry and RT-PCR.
The expression of PECAM-1 protein and mRNA was decreased and the lowest level was reached at 8 h and 16 h post injection, respectively. The average values were 95.1 +/- 9.76 and 0.861 +/- 0.016, respectively, which were significantly lower than those in the control group (129.5 +/- 6.15, 1.192 +/- 0.035, P < 0.01). The expression of t-PA and PAI-1 mRNA was increased after LPS was injected. The highest level of t-PA mRNA expression was observed at 2 h after injection. The average value was 1.195 +/- 0.036, which was significantly higher than that in the control group (0.781 +/- 0.017, P < 0.01). The highest level of PAI-1 mRNA expression was observed at 2 h, 4 h and 8 h post injection. The average values were 1.178 +/- 0.069, 1.153 +/- 0.036 and 1.176 +/- 0.044, respectively, which was significantly higher than those of the control group (0.681 +/- 0.019, P < 0.01).
The expression of PECAM-1 protein and mRNA was decreased after LPS injection, suggesting the disruption of the tissue protective mechanism; the expression of t-PA and PAI-1 mRNA was increased, indicating the presence of a hypercoagulability state. At the same time, the expression of t-PA mRNA was increased which caused the extra-cellular matrix degradation at the early phase after LPS injection. These three phenomena might be the contributory factors to pulmonary hemorrhage.