Nitric oxide synthase inhibitor reduces airway inflammation in mouse models with asthma

Abstract

Objective To explore the therapeutic effect of nitric oxide synthase (NOS) inhibitor in asthmatic mice. Methods BALB/c mice of 5 to 6 weeks were randomly divided into five groups with 10 in each: 1)control group; 2)asthma group: The asthma model was established by ovalbumin (OVA)-sensitized mice; 3)S-methyl isothiourea sulfate (SMT) group: OVA-sensitized asthmatic mice were stimulated and then given with SMT; 4)N-nitro-L-arginine methyl ester (L-NAME) group: OVA-sensitized asthmatic mice were stimulated and then given with L-NAME; 5) NG-monomethyl-L-arginine (L-NMMA) group: OVA-sensitized asthmatic mice were stimulated and then given with L-NMMA. HE staining was used for histopathological analysis. Airway reactivity was assessed using a methacholine challenge test. The levels of nitric oxide (NO) and cytokines in serum and bronchoalveolar lavage fluid(BALF) were detected by ELISA. Results Compared with the control group, goblet cell proliferation and increased mucus secretion were found in the asthma group, together with a large number of inflammatory cell infiltration around the trachea and blood vessels and significantly increased airway resistance, which were improved after the administration of NOS inhibitors, especially in the SMT group. Compared with the control group, the levels of NO in plasma, BALF and lung tissue homogenate were significantly increased in the asthma group (P＜0.05), while the level of IL-2, IL-4, IL-17 and TNF-α in plasma and BALF was significantly increased (P＜0.05). Compared with the asthma group, the level of NO in plasma, BALF and lung tissue homogenate was significantly decreased in SMT group (P＜0.05), while the level of IL-2, IL-4, IL-17 and TNF-α in plasma and BALF was significantly decreased in SMT group (P＜0.05). Compared with the asthma group, the level of plasma NO, IL-2, IL-17, and TNF-α in the L-NAME group was significantly decreased (P＜0.05). The level of NO, IL-2, IL-17, and TNF-α in BALF was significantly decreased (P＜0.05). Compared with the asthma group, the plasma level of NO, IL-2, IL-4, IL-17 and TNF-α in the L-NMMA group was significantly decreased (P＜0.05). The level of NO, IL-2, IL-4, IL-17 and TNF-α in BALF was significantly decreased(P＜0.05), and the level of NO in lung tissue homogenate was significantly decreased (P＜0.05). Conclusions NOS inhibitor, especially SMT may reduce airway inflammation of asthmatic mice.

Keywords

• asthma|nitric oxide|nitric oxide synthase|inhibitor