氨溴索预先给药对兔单肺通气时肺损伤的影响

Effects of ambroxol pretreatment on the lung injury during one-lung ventilation in rabbits

目的评价氨溴索预先给药对兔单肺通气时肺损伤的影响。方法家兔67只随机分为4组，麻醉下气管插管，机械通气，A组（n=18）持续双肺通气4h，B组（n=16）、C组（n=15）和D组（n=18）单肺通气2h后恢复双肺通气2h，C组和D组在单肺通气前分别静脉注射氨溴索5、15mg／kg（生理盐水稀释至20ml），B组给予等容量生理盐水。分别于麻醉前（基础状态）、单肺通气1、2h、恢复双肺通气1、2h时采集静脉血样，测定血清超氧化物歧化酶（SOD）活性、肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）和IL-8浓度，进行白细胞（WBC）计数和中性粒细胞计数，最后一次采集血样后，处死动物，取双侧肺组织，光镜下观察肺组织病理学。结果与A组比较，B组、C组和D组SOD活性降低，TNF—α、IL-6、IL-8、WBC计数和中性粒细胞计数升高（P〈0．05或0．01）。与B组比较，C组和D组SOD活性升高，TNF—α、IL-6、IL-8、WBC计数和中性粒细胞计数降低（P〈0．05或0．01）。C组和D组间上述指标差异无统计学意义（P〉0．05）。A组双侧肺组织未见明显损伤；C组和D组非通气侧肺组织损伤轻于B组。结论静脉注射氨溴索5、15mg／kg可减轻单肺通气诱发兔肺损伤，其机制与抑制炎性反应及脂质过氧化反应有关。

Objective To investigate the effects of ambroxol pretreatment on the lung injury during onelung ventilation （OLV） in rabbits. Methods Sixty-seven rabbits of both sexes weighing 2.0-2.5 kg were randomly divided into 4 groups： group A two-lung ventilation （TLV） （ n = 18） ; group B OLV （ n = 16） ; group C ambroxol 5 mg/kg ＋ OLV（ n = 15） and group D ambroxol 15 mg/kg ＋ OLV （ n = 18）. The animals were anesthetized with intramuscular ketamine 25 mg/kg, traeheostomized and mechanically ventilated （FiO2 1.0, I ： E 1 ： 2, during TLV VT 10 ml/kg, RR 35 bpm, during OLV VT 7 ml/kg, RR 55 bpm）. Bilateral lungs were ventilated for 4 h in group A. In group B, C and D unilateral lung was ventilated for 2 h followed by 2 h TLV. In group C and D ambroxol 5 and 15 mg/kg in normal saline （NS） 20 ml were given IV before OLV respectively while in group B equal volume of NS was given instead of ambroxol. Venous blood samples were taken before mechanical ventilation was started at 1 and 2 h of OLV and 1 and 2 h of TLV respectively for determination of serum SOD activity and serum TNF-α, IL-6 and IL-8 concentrations and WBC and neutrophil granuloeyte count. The lungs were then removed for microscopic examination. Results The serum SOD activity was significantly lower and TNF-α, IL-6 and IL-8 concentrations and WBC and neutrophil granulocyte counts were significantly higher in group B, C and D than in group A. Serum SOD activity was significantly higher and serum TNF-α, IL-6 and IL-8 concentrations and WBC and neutrophil granulocyte counts were significantly lower in group C and D than in group B： There was no significant difference in the serum SOD activity, TNF-α, IL-6 and IL-8 concentrations and WBC and neutrophil granulocyte counts between group C and D. The damage to the non-ventilated lung tissue was significantly ameliorated in group C and D as compared with group B. Conclusion Ambroxol 5 and 15 mg/kg iv can attenuate the lung injury during OLV by inhibiting inflammatory response and lipid peroxidation.