| Objective To explore the pathogenesis of acute lung injury in rats suffering hemorrhagic shock at plateau. Methods Seventy-two male Wistar rats, weighing 280-320 g, were randomized into 6 groups (n=12): sham group (group Sham), hemorrhagic shock for 15 min (group HS15), hemorrhagic shock for 30 min group (group HS30), hemorrhagic shock for 45 min group (group HS45), hemorrhagic shock for 60 min group (group HS60) and 90 min group (group HS90). Hemorrhagic shock model of Wistar rats was reproduced at plateau. The rats were only anesthetized, no shock and were sacrificed after 90 min in group Sham. The other groups were different in bleeding time and then were respectively sacrificed at 15, 30, 45, 60 and 90 min after shock. The pathological changes in the lungs were observed with light microscope. Wet to dry weight ratio (W/D), lung permeability index (LPI), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and superoxide dismutase (SOD) in lung were measured. Enzyme linked immunosorbent assay was used to detect the TNF-α and IL-10 in lung tissue, the expression and distribution of claudin-3 and claudin-4 in lung tissue was verified by immunohistochemistry method. Results Compared with group Sham, shock causes acute lung injury at different degree, and was positively correlated with the duration of shock, during the period of 15 to 30 min, it merely rendered a slight change in lung W/D, LPI, MPO, MDA, TNF-α, T-SOD and IL-10. Subsequently, along with time prolonged, lung W/D, neutrophils in BALF, LPI, MPO, MDA, TNF-α were significantly elevated, while T-SOD and IL-10 were notably reduced (P<0.05). Immunohistochemical results showed that claudin-3 and claudin-4 expression in lung epithelial cells and endothelial cells expressed at low levels and dislocated (P<0.05). Conclusion After a short time compensatory lesions, the change of rats’ hemodynamic stability suffering severe hemorrhagic shock showed a spiral downward. Along with the extension of the shock, hemorrhagic shock at plateau results into the disturbance of inflammatory response and oxidative stress, the loss of claudin-3 and claudin-4 in lung epithelial cells, which triggers the acute lung injury. |
