| Objective The present study was to observe the effect of inhaling ketamine on the airway inflammation in an asthma model in Sprague Damley (SD) rats and to explore its possible mechanisms.Methods Forty SD rats were randomly assigned to five groups with eight rats each: Those are control group (group N), asthma model group (group A) and three pretreated groups with different concentrations of ketamine ( group K1, K2, K3 ). The rats in group A were sensitized by injection of ovalbumin (OA) together with aluminum hydroxide and Bordetella pertussis as adjuvants. Two weeks later followed by aerosolized OA challenge 20min a day for seven consecutive days. The rats in Kl, K2 and K3 groups were sensitized with OA and adjuvants as in group A, but exposed to an aerosol of ketamine of 12.5mg/ml, 25mg/ml and 50mg/ml concentration respectively before challenge with OA. The rats in group N received 0.9% sterile saline by injection and inhalation. 24hrlater after the last challenge, the rats were exsanguinated of the abdominal aorta. One part of the blood samples was centrifuged immediately for isolation of lymphocytes and cytosolic and membrane PKC fractions were extracted, then PKC activities were determined by the incorporation of 32P from y -32P-ATP into Histone (III-S). Another part of the blood samples was centrifuged and the supernatant was obtained for assay of interleukin-4 (IL-4) by ELISA. The rats were killed finally, and the left main bronchia were seperated immediately and lavaged with 0.9% sterile saline, then total cells were counted in the brochoalveolar lavage fluid (HALF). At the same time, the right lung (not lavaged) of the rats in each group was removed for histopathologic examination.Results (1) The amount of total leucocytes in BALF increased significantly in the rats of group A, and was no significantly difference between group Kl and group A. The amount of total leucocytes in group K2 and K3 was lower than that in group A (P < 0.01, P < 0.05 respectively). (2) Histopathologic changes of the lung in group N showed that the structure of small bronchi, bronchioles and lung alveoli was normal, the epithelia of mucosa was integral. The acute inflammation changes in the airway of group A were observed, including that the creases of mucous membranes in small bronchi and bronchioles obviously decreased, bronchial epithelia damaged and shed in different degrees, the structure of lumen in bronchi disrupted, multi-cell infiltration in the bronchial submucosa and surrounding alveolar septum. A few secretions and damaged cells inside lumen of the bronchi and alveoli were observed. There were multi-cell infiltration in the bronchial submucosa and surrounding alveolar septum and a few secretions and damaged cells inside lumen of the bronchi in group Kl. Cell infiltration was rarely seen in group K2. There was less inflammation cells infiltration in the bronchialsubmucosa and surrounding alveolar septum and no local tissue damage was observed in group K3. (3) The plasma IL-4 concentration in the group A was significantly higher than that in the group N (P < 0.01), and there was not obviously different between group K1 and group A. IL-4 concentration was significantly lower in group K2 and K3 than that in group A (P < 0.05). (4) The total (PKCT), cytosol (PKCc), membrane (PKCM) PKC activity and the percentage of membrane PKC (PKCM%) in the rats of group A were significantly higher than that of group N (P < 0.01). There was no difference of PKCT, PKCC, PKCM and PKCM% between group Kl and group A. The lower level activity of PKCT, PKCC, PKCM was observed and the PKCM% decreased in different degrees in group K2 and K3 (P < 0.01, P < 0.05 respectively). (5) There were good positive correlations between the total cells of HALF and concentration of IL-4 and PKCr and PKCM% (r = 0.43, 0.61, 0.67, P < 0.01, respectively) and also good positive correlations between concentration of IL-4 and PKCT and PKCM% (r = 0.57, 0.41, P < 0.01, respectively).Conclusions (1) 25mg/ml or 50mg/ml aerosolized ketamine h...
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