Objective To investigate the expression of the histone deacetylases 1( HDAC1) and the level of whole histone acetylation and methylation in lung T cells of asthmatic rats, and investigate their role in the pathogenesis of asthma.Methods Sixteen wistar rats were randomly divided into a control group and an asthma group( n =8 in each group) . The rats was sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The asthmatic ratmodel was confirmed by measurement of pulmonary function, histochemical staining, HE staining, and the levels of interleukin-4 ( IL-4 ) , interferon-gamma ( IFN-γ) and immunoglobulin E( IgE) in serum and bronchoalveolar lavage fluid ( BALF) . T cells were isolated fromrat lungs and the purity was identified. The expression of the HDAC1, the level of whole histone H3 and H4 acetylation, and whole H3K9 dimethylation were analyzed by Western blot in lung T cells. Results Compared with the control group, the protein expression of HDAC1 was significantly lower( 0. 465±0. 087 vs 0. 790 ±0. 076, P lt;0. 05) in lung T cells of the asthma group. No significant differences werefound in regard to the level of whole histone H3 and H4 acetylation and whole H3K9 dimethylation betweenthe two groups. Conclusions HDAC1 in lung T cells may be involved in the pathogenesis of asthma.Histone modification by HDAC1 may be a specific eventwith gene transcription which may not be associated with asthma.
ObjectiveTo investigate the neuroprotective effects and mechanisms of selective histone deacetylases inhibitor MS-275 on rats after seizures. MethodsA total of 75 rats were randomly divided into 5 groups for treatment:control group,pilocarpine group, treatment group Ⅰ(administered with MS-275, 20mg/kg, once a day,intraperitoneally in 7 consecutive days), treatment group Ⅱ(administered with MS-275, 40mg/kg, once a day, intraperitoneally in 7 consecutive days), MS-275 pretreatment group. We used lithium and pilocarpin to induce seizures. Behaviors of rats in each group were observed. At 72 hours after seizures, Nissl staining and immunohistochemical were respectively used to evaluate the loss of neurons and histone acetylation levels of hippocampal CA1 and CA3 regions in each group. Escape latency in the control group, treatment group Ⅰ, treatment group Ⅱ and MS-275 pretreatment group were longer than pilocarpine group(P<0.05). ResultsCompared with the pilocarpine group, rats in MS-275 pretreatment group could delay pilocarpine-induced seizures and reduce mortality (P<0.05). Degree of neuronal loss and degeneration in both treatment group Ⅰ and treatment group Ⅱ were reduced compared with the pilocarpine group (P<0.05) and the level of histone acetylation in hippocampal CA1 and CA3 regions of the rats were increased compared with the pilocarpine group (P<0.05). ConclusionHDACs inhibitors MS-275 can improve the neuronal damage, histone deacetylation of rats' brain and rats cognitive decline, which can exert an neuroprotective effect on rats after seizures, whose mechanism may be related to its antiinflammatory effect.