关键词: 哮喘, sirtinol, 地塞米松, 沉默信息调节蛋白1, 白细胞介素5

Abstract: BACKGROUND: Asthma is a chronic inflammatory disease of the respiratory tract mediated by a variety of inflammatory cells. Recombinant sirtuin 1 (SIRT1) is closely related to the occurrence of asthma and airway hyperresponsiveness. 
OBJECTIVE: To compare the effects of sirtinol (a specific inhibitor of SIRT1) in different concentrations and dexamethasone on the expression of SIRT1 gene and interleukin-5 in asthmatic mice, and to provide a new theoretical basis for the role of SIRT1 in asthma pathogenesis and related treatments. 
METHODS: Forty-two female Balb/c mice were randomly divided into seven groups: blank control group, asthma group, dexamethasone group, sirtinol group 1, sirtinol group 2, sirtinol group 3, and sirtinol group 4. In the latter six groups, a mouse model of asthma was prepared as follows: mice were intraperitoneally given 0.2 mL of antigen suspension (100 μg of ovalbumin OVA + 2 mg of aluminium hydroxide + 0.2 mL of normal saline) for sensitization on days 1, 8 and 15, and then given 40 μL of 2% ovalbumin solution (2 g of ovalbumin +100 mL of normal saline) via the nasal cavity to stimulate high airway response for 7 continuous days. Mice in the blank control group were given the same volume of normal saline. The dexamethasone group was intraperitoneally injected with 0.2 mL of dexamethasone solution (3 mg/kg) 30 minutes before excitation, and the sirtinol groups 1, 2, 3, and 4 were injected intraperitoneally with 0.12 mL of sirtinol solution at different concentrations (0, 0.05, 0.5, and 3.0 mg/kg), respectively, at 1 hour before first excitation and 3 hours after last excitation. Additionally, the sirtinol group 1 was intraperitoneally injected with 0.12 mL of 0.125% dimethyl sulfoxide solution. The mice were sacrificed 24 hours after the last excitation, and lung tissue morphology was observed by hematoxylin-eosin staining. The expression of SIRT1 in the lung tissue of mice was detected by western blot. The mRNA levels of SIRT1 and internal reference gene (β-actin) in the lung tissue of mice was detected by real-time fluorescence quantitative PCR. Interleukin-5 content in bronchoalveolar lavage fluid was detected by enzyme-linked immunosorbent assay. 
RESULTS AND CONCLUSION: Inflammation was relieved in the dexamethasone group compared with the asthma group, but not significantly in the sirtinol group 1. Inflammation reduction was progressively decreased in the sirtinol groups 2, 3, and 4. Compared with the asthma group, SIRT1 expression was decreased in the dexamethasone group and the sirtinol groups 1, 2, 3, 4, and was lowest in the sirtinol group 2. The expression of SIRT1 mRNA in the lung tissue was highest in the asthma group and lowest in the blank control group. The expression level of SIRT1 mRNA in the asthma group was significantly higher than that of the dexamethasone group, sirtinol group 2 and sirtinol group 3 (P < 0.05). However, there was no significant difference among dexamethasone group, sirtinol groups 2, and sirtinol group 3 (P > 0.05). The interleukin-5 content in the bronchoalveolar lavage fluid was lowest in the blank control group and highest in the asthma group. The interleukin-5 content in the sirtinol group 4 was significantly higher than that in the sirtinol group 2, 3, and dexamethasone group (P < 0.05). However, there was no significant difference among the dexamethasone group, sirtinol group 2, and sirtinol group 3 (P > 0.05). To conclude, both dexamethasone and sirtinol can reduce the expression level of SIRT1 and the content of interleukin-5, and relieve airway inflammation in asthmatic mice. They have similar effects, but the effect of the latter is related to the concentration. 

Key words: asthma, sirtinol, dexamethasone, recombinant sirtuin 1, interleukin-5