排痰液防治呼吸机相关性肺炎动物模型的实验研究

Animal model experimental study on sputum discharge liquid for preventive treatment of ventilator associated pneumonia

目的通过呼吸机相关性肺炎(VAP)实验动物模型,探讨排痰液的安全性及止咳祛痰等作用机制,为该药物治疗(VAP)提供实验依据。方法取小鼠20只,灌胃给药观察小鼠24h内以及7d内死亡情况,计算药物100.0%死亡率剂量、最大耐受剂量(MTD)和LD50值;取小鼠60只,分为6组,分别以灌胃和雾化吸入两种途径给药,通过碳粒廓清法测定药物对小鼠巨噬细胞吞噬功能的影响;取小鼠80只,分为8组,通过小鼠浓氨水引咳实验检测排痰液对反射性咳嗽的止咳作用;取小鼠80只和大鼠64只,分别分为8组,分组同上,通过小鼠气管酚红排泌实验和大鼠黏多糖含量测定实验检测药物的祛痰作用。结果急性毒性实验显示,24h内和7d内均无小鼠死亡;酚红排泌实验和黏多糖测定显示,不同给药方式给药后结果均显示中、高剂量组药物具有促巨噬细胞吞噬功能;小鼠气管酚红排泌量和大鼠气管分泌液中黏多糖的含量与正常对照组比较差异有统计学意义(P<0.05)。结论排痰液可止咳化痰、促巨噬细胞吞噬功能作用,无显著不良反应,较好临床应用价值。

OBJECTIVE To observe the safety of sputum discharge liquid（SDL）for treating ventilator associated pneumonia in animal model and the mechanism of relieving cough and removing sputum so as to provide a clinical reference for this medication for the treatment of VAP.METHODS Totally 20 mice were enrolled and received gastric administration.Death situation of mice was observed within 24 hand 7dto calculate 100.0% mortality dose,maximum tolerated dose（MTD）and LD50 values.Another 60 mice were enrolled and divided into 6groups which received the medicine by gastric administration or atomization inhalation.The carbon clearance method was used to determine the effect of the medicine on macrophage phagocytosis in mice.Another 80 mice were enrolled and divided into eight groups to test the antitussive effect of sputum discharge liquid on reflexive cough through experiment of concentrated ammonia induced cough in mice.In addition,80 mice and 68 rats were selected and divided into eight groups as above to test the expectorant effect of the medicine through the phenolsulfonphthalein excretion experiment and the glycosaminoglycan content assay.RESULTS Acute toxicity experiments showed that no death occurred within 24 hand 7d.The phenolsulfonphthalein excretion experiment and the glycosaminoglycan assay showed both middle and high doses promoted the phagocytosis of macrophages after administration by different routes.There were significant differences in the phenolsulfonphthalein excretion amount in mouse trachea and the mucopolysaccharide content in secretions in rat trachea compared with normal control groups（P〈0.05）.CONCLUSION Sputum discharge liquid can be taken orally,possessing effects of relieving cough and removing sputum as well as promoting phagocytosis of macrophages,with no significant toxic adverse reactions.It has significant clinical application value.