不同剂量氯马斯汀预给药对大鼠机械通气肺损伤炎性反应的影响

Pre-administration effect of different doses of clemastine on pulmonary inflammatory response in rats with mechanical ventilator-induced lung injury

【目的】评价不同剂量组胺H1受体拮抗剂氯马斯汀对大鼠机械通气相关性肺损伤(ventilator-induced lung injury,VILI)炎性反应的影响。【方法】清洁级健康雄性SD大鼠50只,体质量250~300 g,9~10周龄,采用随机数字表法分为5组(n=10)。麻醉开始前30 min,假手术组(S组)、机械通气肺损伤组(V组)肌肉注射1.8 ml/kg生理盐水;氯马斯汀预给药组(Cle1~3组)分别给予氯马斯汀0.45、0.90、1.80 mg/kg(浓度分别为0.25、0.50、1.00 mg/ml)肌肉注射。麻醉后行气管插管术,S组保留自主呼吸,V组、Cle1~3组机械通气参数设置为VT40 ml/kg,呼吸频率40次/min,通气时间4 h。通气结束处死大鼠,采用ELISA法测定支气管肺泡灌洗液(broncho alveolar lavage fluid,BALF)中白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)浓度,计数BALF中嗜酸性粒细胞(eosinophils,EOS),HE染色行肺组织病理学检查,测量肺湿重/干重(wet to dry ratio,W/D)比值。【结果】与S组比较,V组、Cle1~3组BALF中IL-6、TNF-α浓度升高(P<0.05)、EOS计数增多(P<0.05),W/D比值增高(P<0.05);与V组比较,Cle2、3组BALF中IL-6浓度、TNF-α浓度、EOS计数、W/D比值均降低(P<0.05);Cle1~3组组内比较,BALF中IL-6、TNF-α浓度随剂量增加依次降低,与Cle2组比较,Cle3组W/D比值改变无统计学意义(P>0.05)。【结论】氯马斯汀预给药在大鼠VILI中起到一定抗炎作用,其效果与剂量有一定相关性,0.90 mg/kg效果最佳。

【Objective】To evaluate the effect of different doses of histamine H1 receptor(H1R) antagonist, clemastine, on the inflammatory responseto mechanical ventilator-induced lung injury(VILI) in rats.【Methods】Fifty cleaning-grade healthy male SD rats weighing 250-300 g and aged 9-10 weeks were randomly divided into 5 groups(n=10): sham operation group(group S), mechanical ventilation-induced lung injury group(group V) and clemastine pre-administration groups(groups Cle1-3). Therats in groups Cle1-3 weretreated with intramuscular injection of 0.45, 0.9 and 1.8 mg/kg(the concentrations were 0.25, 0.5 and 1 mg/ml, respectively) of clemastine, and the rats in the group S and group V were given 1.8 ml/kg of normal salinevia intramuscular injection 30 minutes before the beginning of anesthesia. After anesthesia, the rats were treated with endotracheal intubation. The rats in the group S retained spontaneous breathing, while those in thegroup V and groups Cle1-3 were treated with mechanical ventilation. The ventilation parameters were set ata volume tidal(VT) of 40 ml/kg, respiratory rate 40 times/min for 4 hours. After ventilation, the concentrations of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid(BALF) were measured by ELISA,eosinophils(EOS) in BALF were counted, lung histopathology was examined by HE staining, and wet/dry lung weight(W/D) ratio was measured.【Results】Compared with group S, the concentrations of IL-6, TNF-α and EOS countin BALF were increasedand W/D ratio increased in groups V and Cle1-3(P<0.05). Compared with group V, the concentrations of IL-6, EOS count in BALFand W/D ratio ingroup Cle2 and 3 were decreased(P<0.05). The concentrations of IL-6, TNF-αin BALFwere decreased with increasing dose betweengroups Cle2-3(P<0.05). Compared with group Cle2, W/D ratio in group Cle3 was not statistically significant(P>0.05).【Conclusion】Pre-administration of clemastine may play ananti-inflammatory role in the lung of VILI rats. The effect may be related to the dose, and 0.9 mg/kg is the best.