Effect Of Nebulized Ketamine On Airway Hyperresponsiveness And The Expression Of Nuclear Factor κB In Allergic Asthma Rats

Objective: To investigate the effect of nebulized ketamineinhalation on airway hyperresponsiveness and the expression of NuclearfactorκB in allergic asthma rats.Methods: Forty male Brown Norway rats were randomized into fivegroups: control group (group C), asthma model group (group A), threepretreatment groups of different concentration of ketamine (group K1,K2, K3 ) with eight rats each. The rats in group A were sensitized byinjection of ovalbumin (OVA) together with aluminum hydroxide andBordetella pertussis as adjuvants, two weeks later followed byaerosolized OVA(1%) challenge for 30 min. The rats in group K1,K2,K3 were sensitized with OVA the same as those in group A, but exposed toaerosol ketamine 12.5,25,50 mg/ml for 30 min before exposed toaerosol OVA.The rats in group C were injected and inhaled with the samedose PBS. All rats were studied 24 h after exposure to either 1% OVA orPBS aerosol. Airway responsiveness were assessed using a whole bodyplethysm graphy. The right main bronchia in each group were separatedimmediately and the right lung of the rats was removed. RT-PCR wasused to dectect the mRNA expression of Nuclear factorκB. the left lunglobes was removed for histopathologic examination and the expression ofNuclear factorκB levels in the lung tissue in asthma model rats wasobserved by immunohistochemical staining.Results: (1) The increase of Re in group K1,K2 and K3 wassignificantly lower than that in group A when ACH dose with 50ug/kg,100 ug/kg,200 ug/kg(P＜0.01).The decrease of Cldyn in groupK1,K2 and K3 was significantly compared with group A when ACH dosewith 50 ug/kg,100 ug/kg,200 ug/kg(P＜0.01). (2) The Nuclear factorκBP65 mRNA expression and Nuclear factorκB levels in asthma group wassignificantly higher than that of control group(P＜0.05), K1,K2 and K3group significantly lower than asthma group(P＜0.05). (3) There wereacute airway inflammation changes in group A. Compared with group A,there was significantly less inflammation in the bronchial subnucosa andalveolar septum in group K1,K2 and K3. Conclusions: Inhalation of nebulized ketamine could effectivelydecrease airway inflammation by inhibiting activation of Nuclear factorκB and alleviate the airway hyperresponsiveness in allergic asthma rats.