氯胺酮雾化吸入对哮喘大鼠气道反应性和炎症的影响

Effect of aerosolized ketamine on airway responsiveness and inflammation in allergic asthma rats

目的观察氯胺酮雾化吸入对哮喘模型大鼠气道反应性和炎症的影响。方法将40只Brown Norway大鼠随机分成对照组(C组)、哮喘模型组(A组)、氯胺酮1组(K1组)、氯胺酮2组(K2组)、氯胺酮3组(K3组),每组8只。A组用卵蛋白辅以百日咳杆菌菌苗及氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发;K1,K2,K3组大鼠以同样方法致敏,在激发前分别雾化吸入12.5、25、50 mg/mL的氯胺酮;C组注射和雾化吸入PBS。应用动物体描箱法测定大鼠的气道反应性,计数支气管肺泡灌洗液(BALF)中细胞总数并分类,检测BALF中IL-13浓度(ELISA法)。结果在乙酰胆碱(ACH)浓度为50、100、200μg/kg时,K1、K2、K3组呼气阻力(expiratory resistance,Re)的明显小于A组(P<0.05),与哮喘组比较,治疗组BALF中白细胞总数、嗜酸细胞的数目、BALF中IL-13水平明显下降(P<0.05)。结论氯胺酮雾化吸入治疗可明显减轻哮喘模型大鼠气道反应性和气道炎症。

Objective To investigate the effect of aerosolized ketamine on airway hyperre- sponsiveness and inflammation in allergic asthma rats . Methods Forty Brown Norway rats（ 10 - 12 weeks）were randomly assigned to five groups with eight animals each, control group（C）, asthma group（A） ,and ketamine pretreated groups（K1, K2, K3）. In group A, KI, K2, K3, asthma was induced in two steps： receiving subcutaneous injection of ovalbumia（OVA） and aluminum hydroxide, and then inhaling nebulized 1% OVA in PBS for 30 min. In group K1, K2 and K3, the sensitized rats were exposed to 12.5 mg/mL（K1 group）, 25 mg/mL（K2 group）, 50 mg/mL（K3 group） of nebulized ketamine for 30 min. Airway responsiveness was assessed using a whole body plethysm graphy. BALF of five groups were collected. The differential white cell count in BALF was conducted. The concentrations of IL- 13 in BALF were measured by enzymelinked immunosorbent assay Results The increase of Re in group K1, K2 and K3 was significantly lower than that of the group A when ACH dose with 50μg/kg, 100μg/kg and 200μg/kg （P 〈 0.05）. Compared with group A, the counts of total cell and eosinophil in BALF were significantly reduced in group K1, K2 and k3 （P 〈 0.05）. The concentrations of IL- 13 in BALF were significantly reduced in group K1, K2 and K3 （P 〈 0.05）. Conclusion Aerosolized ketamine could effectively alleviate the airway hy- perresponsiveness and inflammation in allergic asthma rats.