大剂量表面活性物质和地塞米松联用对大鼠百草枯中毒急性肺损伤的治疗作用

目的:评估表面活性物质单独或联合地塞米松气管内给药对百草枯诱导的大鼠急性肺损伤(ALI)的治疗作用。方法:成年雄性SD大鼠50只,腹腔内注射百草枯(35mg/kg)建立ALI模型,随机分5组,不同剂量表面活性物质气管内给药治疗:Ⅰ组:50mg/kg,Ⅱ组:100mg/kg,Ⅲ组:50mg/kg,Ⅳ组:100mg/kg,Ⅲ组和Ⅳ组:分别同时联合应用地塞米松(0.5mg/kg);Ⅴ组为对照组:等体积无菌生理盐水。检测各组不同给药时间血氧饱和度、测肺容积及支气管肺泡灌洗液中炎症细胞、总蛋白含量。结果:与对照组相比,Ⅱ、Ⅲ、Ⅳ组血氧饱和度显著提高(P<0.05),Ⅳ组肺容量显著增加(P<0.05),支气管灌洗液中炎症细胞总细胞数、巨噬细胞数和中性粒细胞明显降低(P<0.05),Ⅱ组和Ⅳ组中蛋白含量减少70%(P<0.05);与Ⅱ组相比,Ⅳ组总细胞数和中性粒细胞、巨噬细胞数明显减少(P<0.05),蛋白含量进一步减少(P<0.05)。结论:大剂量表面活性物质与地塞米松联用治疗大鼠ALI,能提高气体交换,减轻肺的炎症反应,疗效明显优于单独应用表面活性物质或小剂量表面活性物质与地塞米松联用。

The Therapeutic Effect of the Combined Administration of High Doses of Surfactant and Dexamethasone on Paraquat-induced Acute Lung Injury in Rats

Objective To evaluate pulmonary responses to intratracheal administration of surfactant with and without dexamethasone in rats with paraquat-induced lung injury. Methods Fifty adult SD rats were randomly divided into 5 groups. ALI models were established wuth paraquat intraperitoneal injection (35mg/kg). Three days later, tracheotomy tube was adopted and began artifical ventilation. Different intratracheal administration proposals were adopted. In group Ⅰ and Ⅱ, surfactant was solely administrated with different doses (50mg/kg in group Ⅰ and 100mg/kg in group Ⅱ). In group Ⅲ and Ⅳ, different doses of surfactant (50mg/kg in group Ⅲ and 100mg/kg in group Ⅳ) combining with dexamethasone (0.5 mg/kg) were adopted. Group Ⅴ was served as control group, equal volume of saline was used. Hemoglobin oxygen saturation was detected 60 min and 90 min after treatment. Subsequently, lung volume was measured.Then,bronchoalveolar lavage fluid was collected and the number of inflammatory cells and the quantity of protein were detected. Results Compared with group Ⅴ, the hemoglobin oxygen saturation of group Ⅱ, Ⅲ and Ⅳ were significantly enhanced. Furthermore, in group Ⅳ, the count of total cells, neutrophilic granulocytes, macrophages in bronchoalveolar lavage fluid were significantly descreased,the lung volumes were increased, and the protein in bronchoalveolar lavage fluid in group Ⅱ and Ⅳ was decreased. Conclusion In rat models with paraquat-induced lung injury, high doses of surfactant combining with dexamethasone could markedly promote air exchange, relieve inflammatory response and lung injury ,and the therapeutic effect is better than solely surfactant or low doses surfactant combining with dexamethasone.