| Backgroud and objectiveDespite advances in supportive care, the mortality rate in patients with acute lung injury (ALI)/acute respiratory distress syndrome still remains high. At present, the scholars from home and abroad widely consider the systemic inflammatory response (SIR) plays a key role in the development of ALI/ARDS. While in parallel to the inflammatory response, the body mounts a compensatory anti-inflammatory reaction (CAR) in order to counter inflammatory mediators. If SIR and CAR are dynamically balanced, homeostasis can be restored. So how to enhance CAR and inhibit SIR in order to restore balance and how to interrupt inflammatory cascade reaction have become the focuses of studies on ALI/ARDS. Though the study about ALI/ARDS in neonate is delayed, there were many reports of ARDS in neonate. ALI in neonate has a lot of differences compared with in adults and children. ALI in neonate should not be ignored. The purpose of our study was designed to investigate the kinetics of inflammatory mediators and anti-inflammatory mediators in the development of ALI and to study the protective effect of Penehyclidine Hydrochloride Injection on acute lung injury(ALI) induced by lipopolysaccharide(LPS) in the neonate rats .MethodsA neonate rat model of acute lung injury(ALI) was induced by intraperitineal infection of lipopolysaccharide(LPS 3mg/kg). 40 neonatal Wistar rats were randomly divided into four groups: normal control group( I , n=10), which was treated identically to the LPS group except for the substitution of 0.9% saline for LPS; LPS control group (II , n=10), which received LPS injection intraperitineally; group III(n=10), which received intramuscle injection of Penehyclidine Hydrochloride injection(5mg/kg) before they were induced by intraperitineal infection of LPS(3mg/kg) by 30 minutes; group IV (n=10), which received intramuscle injection of Penehyclidine Hydrochloride injection(5mg/kg) after they were induced by intraperitineal infection of LPS(3mg/kg) by 60 minutes. After 4 hours , they were killed. Then the lungs were removed, left lung was used for measurement of wet/dry lung weight ratio . the lung homogenates were prepared to detect the level of TNF-α,IL-10 by ELISA. Futhermore the lung pathologic structure were observed under the transmission electron microscope.ResultsThe wet/dry lung weight ratio in group II was significantly higher than that in group I,III,IV (p<0.01), The wet/dry lung weight ratio in group III was higher than that in group IV (p<0.05) . The lung in group II became enlarged in volume, and swollen. The blood dots or patches were cbserved. Under the transmission electron microscope, in the type II alveolar epithelial cells, microvilli were decreased or even disappeared , vacuoles were formed in the mitochondria, the basement membrane of the capillary endothelial cells was thinner or was broken in some parts in group II. The pathological changes were attenusted in group IV,III, with the latter being even more improved. The level of TNF-α,IL-10 in the neonatal rats, lungs significantly increased after LPS stimulation (p<0.05, p<0.01) . Treatment with Penehyclidine Hydrochloride injection attenuated the change of TNF-αand the level of IL-10.ConclusionsThese results indicate that Penehyclidine Hydrochloride injection has a protective effect on LPS-induced ALI and the effect is more evident in group which were treated in advance. The mechanism is that Penehyclidine Hydrochloride injection can improve the poor peripheral perfusion, protect the membrane of the cells, inhibit the generation and release of inflammatory cytokine (TNF-α) and cytokine (IL-10) significantly. |
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