The protective effect of hepatocyte growth-promoting factor (pHGF) against hydrogen peroxide-induced acute lung injury in rats.

Abstract

To examine the protective effect of hepatocyte growth-promoting factor (pHGF) in hydrogen peroxide (H(2)O(2))-induced acute lung injury in rats, we observed the pathological changes in lung tissue by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and by light and electron microscopy. We also measured the serum levels of lipid peroxide (LPO). At 6 to 24 h after H(2)O(2) injection, the level of LPO was significantly higher in the H(2)O(2) group than in the H(2)O(2) + pHGF-treated group. This finding indicated that pHGF protected against cell membrane damage in H2O2-induced acute lung injury. Positive TUNEL signals were found in capillary endothelial cells, alveolar epithelial cells, and inflammatory cells. In the H(2)O(2) + pHGF-treated group, TUNEL-positive signals were reduced compared with those in the H(2)O(2) group. This finding indicated that pHGF acts to suppress apoptosis. In the H(2)O(2) group, severe pulmonary edema was seen 3 h after H(2)O(2) injection, and at 24 h, severe atelectasis was seen. In the H(2)O(2) + pHGF-treated group, pulmonary edema was scarcely seen and severe atelectasis was not found. This finding indicated that pHGF acts to suppress both severe pulmonary edema and atelectasis. In the H(2)O(2) group, the formation of subendothelial blebs and disruption of endothelial cells was observed. Edema and disruption were seen in type I epithelial cells. In type II lung epithelial cells, mitochondria were swollen and microvilli had disappeared. In the H(2)O(2) + pHGF-treated group, the formation of subendothelial blebs was seen, but no severe subendothelial blebs were observed. Disruption of capillary endothelial cells and type I epithelial cells was not evident, nor was there damage to type II lung epithelial cells. These findings indicated that pHGF protects the progression of H(2)O(2)-induced acute lung injury, and showed that pHGF acts to stabilize the cell membrane in capillary endothelial cells and lung epithelial cells.