盐酸戊乙奎醚对失血性休克-内毒素打击鼠肺损伤的保护作用

[摘 要] 目的 研究盐酸戊乙奎醚（PHC）对失血性休克-内毒素打击所致鼠肺损伤的保护作用。 方法 45只Wistar大鼠随机分为5组：假手术组（S组），失血-内毒素打击模型组（C组），PHC1组(1mg/kg)，PHC2组(2 mg/kg)，PHC3组(3 mg/kg)。在失血性休克“首次打击”基础上，股静脉注入内毒素(LPS)2mg/kg作为“第二次打击”建立失血性休克-内毒素打击急性肺损伤模型。模型成功后股静脉注射PHC，注射PHC2h后，取肺组织测定超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶（MPO）含量及湿干重比（W/D），取动脉血液3ml测血清肿瘤坏死因子-a（TNF-α）、白介素-1（IL-1）、白介素-8（IL-8）含量，光镜下观察肺组织病理改变。 结果 （1）与S组比较，C组与PHC各治疗组肺组织SOD减少（p< 0. 01），MDA和MPO增加（p< 0. 05或p< 0. 01），血清TNF-a、IL-1、IL-8含量均升高(p< 0. 01)；肺组织W/D上升（p< 0. 05），光镜下均出现不同程度的病理改变；（2）与C组比较，PHC各治疗组肺组织SOD增加（p< 0. 05），MDA和MPO减少（p< 0. 05），血清TNF-a、IL-1、IL-8含量均降低（p< 0. 05），肺组织W/D下降（p< 0. 05），光镜下病理损伤减轻；（3）与PHC2组、PHC3组相比，PHC1组肺组织SOD增加（p< 0. 05），MDA和MPO含量减少（p< 0. 05），血清TNF-a、IL-1、IL-8含量较低（p< 0. 05），肺组织W/D下降（p< 0. 05），PHC1组肺组织损伤较PHC2及PHC3组轻。PHC2组与PHC3组比较，SOD、MDA、MPO、TNF-a、IL-1、IL-8及W/D差异无统计学意义（p> 0. 05）。 结论 PHC对失血性休克-内毒素打击所致鼠肺损伤具有保护作用，以1mg/kg较好。

Protective effects of penehyclidine hydrochloride against hemorrhagic shock-endotoxin challenge induced acute lung injury in rats

Protective effects of penehyclidine hydrochloride against hemorrhagic-endotoxin hit induced acute lung injury LIN Chun-shui, CHEN Dong-ting,GU Miao-ning,et al. Department of Anesthesiology, Nanfnag Hospital,Southern Medical University,Guangzhou 510515,ChinaAbstact 　Objective To investigate the protective effects of penehyclidine hydrochloride (PHC) against hemorrhagic-endotoxin hit induced acute lung injury (ALI). Methods 45 wistar rats were randomly assigned to five groups，with 9 animals in each group: sham group(S), control group(C), PHC1 group（1mg/kg，iv）, PHC2 group（2mg/kg，iv）, PHC3 group (3mg/kg，iv).The models of ALI were made by hemorrhagic shock as ‘the first hit’ and then administered LPS (2 mg/ kg) as ‘the second hit’.Lung tissue and blood samples were collected 2h after PHC intravenous injection. The changes of lung tissue superoxide dismutase（SOD ）activity, myeloperoxidase (MPO) activity ,malondialdehyde (MDA ) and wet to dry weigh ratio (W /D ) were examined .The concentration of blood serum tumor necrosis factor-α ( TNF-α) , interleukin 8 (IL-8) and interleukin 1 (IL-1) were analysed by Liquidchip method. Lung histopathological changes were observed by light microscope. Results (1) Compared with group S, group C and PHC groups SOD activity decreased（p< 0. 01）, MDA content and MPO activity increased (p<0.05 or p<0.01);the concentration of serum TNF-α,IL-1 and IL-8 raised（p<0.01），W/D increased (p<0.05); lung tissue were damaged;（2）Compared with group group C, PHC groups SOD activity increased ( p <0.05), MDA content and MPO activity decreased（p< 0.05）; TNF-α,IL-6,IL-8 reduced（p< 0.05）;W/D markedly decreased (p <0.05);lung tissue damage were lessened.（3）Compared with PHC2 and PHC3, group PHC1 SOD activity increased (p < 0.05), MDA content and MPO activity reduced (p<0.05), TNF-α,IL-1 and IL-8 of group PHC1 were decreased (p<0.05), W/D decreased (p <0.05); no significant differences for SOD, MPO, MDA, TNF-α,IL-1,IL-8 and W/D were found between group PHC2 and group PHC3 （P>0.05）, lung tissue damage in group PHC1 were lesser than group PHC2 and group PHC3. Conclusion PHC has the protective effects against lung injury resulting from hemorrhagic-endotoxin hit in rats and the dose of 1mg/kg is better.