氯胺酮雾化吸入对哮喘大鼠气道炎症的影响

Effect of nebulized ketamine on the airway inflammation in a rat model of asthma

目的 观察氯胺酮雾化吸入对哮喘大鼠气道炎症的影响及其机制。方法 雄性SD大鼠40只,随机分成对照组(N组)、哮喘模型组(A组)和不同浓度氯胺酮预处理组(K1组、K2组和K3组),每组8只。A组用卵蛋白(OA)辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,两周后雾化吸入OA激发。K1、K2、K3组大鼠以同样方法致敏,但在激发前分别雾化吸入氯胺酮12.5、25、50mg／ml。N组注射和吸入生理盐水。取血分离淋巴细胞,检测胞浆和胞膜内蛋白激酶C(PKC)的活性,并作肺组织病理学检查。结果 A组肺组织切片显示为急性气道炎症性病理改变。K1组气道壁上皮细胞脱落、结构破坏、炎性细胞浸润等改变多见。K2组支气管壁、肺泡间隔仅见少量的炎症细胞。K3组气道黏膜上皮水肿脱落、黏膜下炎症细胞浸润等程度减轻。与N组比较,A、K1、K3组淋巴细胞PKC总活性(PKCT)、胞浆PKC活性(PKCC)、胞膜PKC活性(PKCM)及PKCM％(PKCM占PKCT的百分比)均增高(P<0.01),K2组PKCT、PKCC、PKCM增高(P<0.01)、PKCM％差异无显著性(P>0.05)。与A组比较,K2、K3组PKCT、PKCC、PKCM及PKCM％均减低(P<0.05或0.01),K1组PKCT、PKCC、PKCM均降低(P<0.01)、PKCM％差异无显著性(P>0.05)。结论 雾化吸入氯胺酮25 mg／ml或50 mg/ml通过PKC途径而发挥抗炎效应。

Objective To investigate the effect of nebulized ketamine inhalation on the airway inflammation in a rat model of asthma and to elucidate the possible mechanism. Methods Forty male SD rats weighing 160-200 g were randomly assigned to one of five group with eight animals in each group: Ⅰ control group (N);Ⅱ asthama group(A)and Ⅲ, Ⅳ,Ⅴ ketamine pretreatment groups ( K1, K2, K3 ). In group Ⅱ-Ⅴ asthma was induced in two steps; (1) the animals received subcutaneous injection of ovalbumia (OA) 1 mg and aluminum hydroxide 160 mg in 1 ml of normal saline (NS) and intraperitoneal devitalized Bordetella pertussis 6 ×109 in 1 ml NS;(2) 2 weeks later asthma was elicited by nebulized 1% OA in NS for 20 min.In group K1,K2 and K3 the sensitized animals were exposed to nebulized ketamine 12.5 mg·ml-1(K1) ,25 mg·ml-1(K2) or 50mg·ml-1(K3) for 20 min,25 min before challenge with nebulized OA.Blood samples were taken and lymphocytes were isolated and cytosol and membrane PKC fractions extracted by centrifugation and PKC acdvities were determined. The right lung was removed for microscopic examination. Results There were acute inflammatoty changes in the airway in group A and there was no significance in the inflammatory cell infiltration in and local damage to the airway between group A and K1. Compared with group A there was significantly less inflammation in the bronchial subnucosa and alveolor septum and no damage was observed in group K2 and K3. The total (PKCT ), cytosol (PKCC) and membrane ( PKCM ) PKC activity and percentage of membrane PKC [( PKCM/PKCT ( % ) ] were significantly higher in group A,K1 and K3 than those in group N ( P < 0.01) .Conclusion Inhalation of nebulized ketamine 25 mg·ml-1 or 50 mg·ml-1 has a protective effect on airway against inflammation and tissue damageinduced by allergen challenge. Ketamine attenuates the capacity of PKC translocation, implying that nebulized ketamine inhalation may exert anti-inflammatory efiects via PKC signal transduction pathway. Nebulized ketamine 25 mg·ml-1 seems to be more effective than 50 mg·ml-1 .