摘要目的 评价盐酸戊乙奎醚对肺癌根治术患者非通气侧肺损伤时Toll样受体4(TLR4)/NF-κB信号通路的影响.方法 拟行肺癌根治术患者100例,年龄40-64岁,BMI 18～27 kg/m2,ASA分级Ⅱ或Ⅲ级.采用随机数字表法分为2组(n=50):对照组(C组)和盐酸戊乙奎醚组(PHC组).PHC组患者于麻醉诱导前10 min静脉注射盐酸戊乙奎醚0.01 mg/kg,C组静脉注射等容量生理盐水.取切除部分肺组织边缘部分,称湿重(W)后烘干,称干重(D),计算W/D比值.光镜下观察肺组织病理学结果和超微结构并行肺损伤评分;采用Western blot法和RT-PCR法分别检测肺组织TLR4和NF-κB及其mRNA的表达.于给药前(T0)、单肺通气即刻(T1)、单肺通气60 min(T2)、单肺通气结束即刻(T3)、术毕(T4)和术后24 h(T5)时分别抽取患者颈内静脉血样,采用ELISA法测定血清TNF-α、IL-6和IL-8的浓度.结果 与C组比较,PHC组患者肺组织W/D比值及肺损伤评分降低,肺组织TLR4和NF-κB及其mRNA表达下调,T2-5时血清TNF-α、IL-6和IL-8浓度降低(P＜0.05).PHC组肺组织病理学及超微结构损伤较C组明显减轻.结论 盐酸戊乙奎醚减轻肺癌根治术患者非通气侧肺损伤的机制与阻断TLR4/NF-κB信号通路,减轻炎症反应有关.

abstractsObjective To evaluate the effect of penehyclidine hydrochloride (PHC) on Toll-like receptor 4 (TLR4) /nuclear factor kappa B (NF-κB) signaling pathway in non-ventilated lung injury in the patients undergoing radical operation for lung cancer.Methods A total of 100 patients,aged 40-64 yr,with body mass index 18-27 kg/m2,of American Society of Anesthesiology physical status Ⅱ or Ⅲ,undergoing radical operation for lung cancer,were divided into 2 groups (n=50 each) according to the random number table method:control group (group C) and PHC group.PHC 0.01 mg/kg was intravenously injected at 10 min before anesthesia induction in group PHC,while the equal volume of normal saline was given instead in group C.The peripheral tissues of the removed lung tissues were obtained for determination of wet/dry weight ratio (W/D ratio).The pathological changes and ultrastructure of lung tissues were observed under light microscope,and lung injury was assessed and scored.The expression of TLR4 and NF-κB protein and mRNA was detected by Western blot and real-time polymerase chain reaction,respectively.Before administration (T0),at the onset of one-lung ventilation (T1),at 60 min of one-lung ventilation (T2),immediately after the end of one-lung ventilation (T3),at the end of operation (T4) and at 24 h after operation (T5),blood samples were collected from the internal jugular vein for determination of serum tumor necrosis factor-alpha,interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.Results Compared with group C,the W/D ratio and lung injury scores were significantly decreased,the expression of TLR4 and NF-κB protein and mRNA was down-regulated,and the concentrations of tumor necrosis factor-alpha,IL-6 and IL-8 were decreased at T12-T5 in group PHC (P＜0.05).The pathological changes and damage to ultrastructure of lung tissues were significantly attenuated in group PHC as compared with group C.Conclusion The mechanism by which PHC attenuates non-ventilated lung injury is related to blocking TLR4/NF-κB signaling pathway and reducing inflammatory responses in the patients undergoing radical operation for lung cancer.