Protective Effect Of Penehyclidine Hydrochloride Pretreatment On Hemorrhagic Shock-Induced Acute Lung Injury In Rats

ObjectiveTo investigate the effects of penehyclidine hydrochloride(PHC) pretreatment on expression of Toll-like receptor 4 (TLR4),p38 mitogen-activated protein kinase in the lung injury induced by hemorrhagic shock in rats, and explore the possible lung protection mechanism of PHC during acute lung injury induced by hemorrhagic shock.MethodsForty healty SD rats of both sexes weighing 200~250g were randomly divided into 5 groups (n=8 each): group A sham operation; group B hemorrhagic shock; group C, D, E received intravenous PHC 0.3, 1.0 or 3.0 mg/kg at 30 min before hemorrhagic shock. The animals were anesthetized with chloral hydrate 3.5ml/kg. Right internal carotid artery was cannulated for MAP monitoring. Left femoral artery was cannulated for bloodletting. Group A did not receive treatment except for cannulatation of femoral artery and vein. The hemorrhagic shock was established by exsanguination from the femoral artery to make mean arterial pressure at 35~45 mmHg within 10min and maintained for 60min. Then the animals were resuscitated with blood transfusion and infusion of normal saline. Except the rats in group A, rest rats were made into hemorrhagic shock models. Group C, D, E received intravenous PHC 0.3mg/kg,1.0mg/kg,3.0mg/kg at 30 min before hemorrhagic shock. The animals were killed at 4h after resuscitation. Their lungs were removed for determination of the expression of TLR-4 mRNA in the lung tissue by RT-PCR and W/D ratio. Expression of p38MAPK,NF-κB in the lung tissue was determined by immuno-histochemical staining. Pathologic change in lung tissue were observed by light microscope.ResultsCompared with group A, in group B there increased obviously TLR4 mRNA and p38MAPK,NF-κB protein expression in lung tissue as well as W/D ratio(P < 0.05 or P < 0.01). Compared with group B, in group D,E there decreased obviously TLR-4 mRNA and p38MAPK,NF-κB protein expression as well as W/D ratio(P < 0.05 or P < 0.01). The lung pathological injury was significantly ameliorated in group D,E as compared to group B under light microscope.ConclusionPHC can attenuate ALI induced by hemorrhagic shock in rats through down regulation of TLR4,p38MAPK expression in the lung.