Effects of penehyclidine pretreatment on nuclear factor kappa B activation during acute lung injury in rats

Objective To investigate the effects of penehyclidine (PHCD) pretreatment on nuclear factor kappa B (NF-κB) activation during acute lung injury (ALI) induced by lipopolysaccharide (LPS). Methods Thirty-five male SD rats weighing 210-280 g were randomly divided into 5 groups (n= 7 each) : group Ⅰ control (C); group Ⅱ ALl; group Ⅲ, Ⅳ,Ⅴ received intraperitoneal (IP) PHCD 0.03, 0.1 and 3.0 mg/kg at 30 min before intravenous LPS. ALI was induced by intravenous LPS 5 mg/kg via tail vein in group Ⅱ- Ⅴ . Normal saline (NS) was given instead of LPS in group Ⅰ . The animals were anesthetized with LP 10% chloral hydrate at 4 h after intravenous LPS. Blood samples were taken from abdominal aorta for blood gas analysis,and PaO2/FiO2 was calculated. The animals were then killed by exsanguination and the lungs were removed for determination of MPO activity in the lung tissue (by colorimetry), W/D lung weight ratio and microscopic examination. Lung homogenate, was prepared for determination of NF-κB activity (by EMSA), expression of TNF-α and IL-β mRNA (by RT-PCR) and protein (ELISA). Expression of NF-κB p65 in the lung tissue was determined by immuno-histochemical staining. Results Compared with control group, PnO2/FiO2 was significantly decreased, while W/D, MPO activity, TNF-α and IL-β mRNA expression and contents and NF-κB activity and protein expression in the lung tissue were significantly increased during ALI induced by LPS in group Ⅱ (P<0.05 or 0.01 ). PHCD pretreatment significantly attenuated the LPS-induced changes in the lung mentioned above in group Ⅲ-Ⅳ. There was no significant difference in the indices mentioned above among group Ⅲ-Ⅴ. Conclusion PHCD pretreatment can ameliorate LPS-induced ALI through inhibition of NF-κB activation and inflammatory response of lung tissue. Key words: Cholinergic antagonists;  NF-κB;  Respiratory distress syndrome, adult