Effect of penehyclidine pretreatment on Toll-like receptor 4 mRNA expression in the lung following acute lung injury induced by hemorrhagic shock in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of penehyclidine (PHCD) pretreatment on Toll-like receptor 4 (TLR4) mRNA expression in the lung following acute lung injury (ALI) induced by hemorrhagic shock in rats. Methods Forty healthy SD rats of both sexes weighing 200-250 g were randomly divided into 5 groups( n = 8 each) group Ⅰ sham operation (group S); group Ⅱ ALI (group ALI); group Ⅲ, Ⅴ, PHCD 0.3,1.0, 3.0 mg/kg were given iv respectively at 30 min before hemorrhagic shock (P1-3). Hemorrhagic shock was induced by exsanguinations. MAP was maintained at 35-45 mm Hg for 60 min. The animals were killed at 4 h after resuscitation. Their lungs were removed for microscopic examination, W/D lung weight ratio and determination of TLR4 mRNA expression in the lung tissue (by RT-PCR). NF-κB p65 protein expression in the lung tissue was determined (by immuno-histochemical staining). Results Hemorrhagic shock significantly increased TLR4 mRNA and NF-κB p65 protein expression in the lung tissue and W/D lung weight ratio. Pretreatment with PHCD 1.0 or 3.0 mg/kg significantly inhibited hemorrhagic shock-induced increase in TLR4 mRNA and NF-κB p65 protein expression in the lung and W/D lung weight ratio. The lung injury was significantly ameliorated in group P2,3 as compared to group ALI. Conclusion PHCD pretreatment can attenuate ALI induced by hemorrhagic shock through down-regulation of TLR4 mRNA expression and decreasing NF-κB activity in the lung.