PHC inhibits sequestration of neutrophils and activation of NF-kappa B in lung tissue of ALI rats induced by LPS
SHEN Wei-feng1,WU Hong-hai2,YANG Bo2,GAN Jian-xin1,JIANG Guan-yu1(1Department of Emergency,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China;2Institute of Pharmacology-Toxicology and Biochemical Pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310031,China.)
AIM: The present study was designed to investigate the effects of penehyclidine hydrochloride(PHC) on lipopolysaccharide(LPS) induced sequestration of neutrophils and activation of NF-κB in lung tissue in rats.METHODS: Acute lung injury was induced successfully by intravenous administraiton of LPS(5 mg/kg) in rats.PHC(3.0,1.0,and 0.3 mg/kg) was administered to rats 0.5 h prior and then again concomitant with LPS exposure. The activity of myeloperoxidase(MPO) and pulmonary microvascular leakage,as indicated by albumin content in the bronchoalveolar lavage fluid(BALF),were measured at 6 h after LPS application.Western blotting analysis was performed to determine the phosphorylations of NF-κB in lung tissue.RESULTS: Challenge with LPS alone resulted in a significant increase in MPO activity and the ratio of neutrophiles in BALF.LPS also triggered activation of NF-κB in 2 h.Pre-treatment with PHC significantly abolished the activation of MPO and increase of neutrophiles in BALF in a dose-dependent manner.Moreover,pretreatment with PHC efficiently blunted the activation of NF-κB induced by LPS at 6 h.CONCLUSION: These results suggested that the protective effect of PHC in LPS-induced ALI in rats was observed,and this effect was partly responsible for the inhibition of the activation of NF-κB by LPS.
【CateGory Index】： R563