Effects of penehyclidine hydrochloride on hemorrhagic shock-induced acute lung injury in rats

Abstract

Objective To observe the effects of penehyclidine hydrochloride (PHC) on hemorrhagic shock/resuscitation-induced acute lung injury in rats.Methods Fifteen healthy adult Sprague-Dawley rats were randomly allocated equally into three groups:groups P,C and S.The rats in group S received sham operation,and those in groups P and C were subjected to bloodletting for shock,then shock state maintained for 60 min,and resuscitation was done with autoblood.The rats in group P received PHC treatment (0.03 mg/kg) before resuscitation of hemorrhagic shock,and those in group C and group S received 1.0 ml normal saline instead.Blood samples were collected via the carotid artery for interleukin-8 (IL-8),tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) monitoring at the time of subsequence carotid arteriopuncture (T0),before shock induction (T1),5 min after shock (T2),before resuscitation of shock (T3),5 min (T4),30 min (T5),1.5 h (T6) and 2.5 h (T7) after mean arterial pressure (MAP) reached expected resuscitation goal.The arterial blood gas analyses were detected at T0,T3 and T7.The morphological changes of lungs were observed under microscope.Results The ratio of PO2/FiO2 in groups P and C were significantly lower than in group S at T7 [(289.5 ± 67.1) mmHg (1 mmHg =0.133 kPa),(280.0 ±73.3) mmHg vs.(458.1 ±31.0) mmHg,P ＜0.01].There was marked diversity among group P,C and S in the morphological score (4.4 ± 1.7,7.4 ± 1.9 vs.0.8 ± 1.1,P ＜0.01) ; The peak concentrations of IL-8 [(7.35 ±0.14),(8.44 ±0.13) ng/L vs.(3.75 ±0.06) ng/L,P ＜0.01],TNF-α [(8.45 ±0.24,(9.69 ±0.52) ng/L vs.(4.19 ± 0.04) ng/L,P＜0.01] and NF-κB [(272.34 ± 12.60),(310.00 ± 16.47) ng/L vs.(133.98 ± 1.91) ng/L,P ＜ 0.01] respectively,with significant difference among three groups.Conclusion Treatment of PHC might have a protective effect against lung injury induced by hemorrhagic shock/resuscitation.Its action mechanisms are probably involved in the suppression of inflammatory factor production and inhibition of the NF-κB pathway. Key words: Hemorrhagic shock ; Acute lung injury; Penehyclidine hydrochloride ; Inflammatory cytokine