Therapeutic effects of histone deacetylase inhibitor givinostat on air inflammation and high airway resistance in a murine asthma model / 中华内科杂志

ABSTRACT

Objective To investigate the therapeutic effects of givinostat , a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation , airway remodeling and airway hyperresponsiveness ( AHR) .Methods BALB/C mice were randomly divided into control group , asthma group, dexamethasone group and givinostat group (n=12 per group).AHR was assessed.Total cell numbers and differential counts , interleukin-4 ( IL-4 ) , interleukin-5 ( IL-5 ) and interferon-γ( IFNγ) levels in the bronchoalveolar lavage fluid ( BALF) were measured in the above 4 groups.The pathology of lung tissue was evaluated .Immunohistochemical ( IHC) staining and Western blot were used to detect αsmooth muscle actin(α-SMA) and transforming growth factor-β1(TGFβ1).Results Compared with the asthma only group, givinostat treatment relieved airway resistance (2.96 ±1.01 vs 6.50 ±0.79,P0.05] was enhanced in BALF.Inflammatory cell infiltration around the airway was reduced , with decreased inflammatory cell score [(1.60 ±0.69) points vs (3.40 ±0.68) points, P <0.01] and inflammatory cell number (111.65 ±31.41 vs 601.25 ±186.85, P<0.01).The goblet cell metaplasia [(26.36 ±2.33)%vs (57.21 ±11.56)%] and collagen deposition area [(52.77 ±7.58)μm2/μm vs (111.81 ±12.40)μm2/μm] were obviously reduced (P<0.01).The expressions of α-SMA and TGFβ1 in the lung tissue were both significantly decreased ( P<0.01 ) .Conclusion Givinostat treatment can reduce airway inflammation , airway remodeling and airway hyperresponsiveness in chronic asthma .Its effect is comparable to that of glucocorticoid hormone treatment .