Effect And Mechanism Of Histone Deacetylase Inhibitor On Delaying Lipopolysaccharide-induced Pulmonary Fibrosis

Lipopolysaccharide(LPS),which is the main components of the endotoxin,is important to cause acute respiratory distress syndrome(ARDS)and pulmonary fibrosis.LPS can activate histone deacetylase enzyme(HDAC)of lung fibroblasts,which will cause the abnormal proliferation and activation,and it is critical for pulmonary fibrosis.Butyric acid is the inhibitor of HDAC.We want to observe while the HDAC is inhibited by butyric acid,how LPS affects the lung fibrosis and its mechanism.Part one Evaluating the effect of histone deacetylase inhibitor on delaying Lipopolysaccharide-induced Pulmonary FibrosisObjective:To evaluate the delay effect of butyric acid,which is the inhibitor of histone deacetylase(HDAC),on lipopolysaccharide(LPS)-induced pulmonary fibrosis.Methods: Mice were randomly divided into 3 groups: Control Group;LPS challenge Group;Butyricacid preconditioning and LPS challenge Group.We take the lung tissue 2 weeks and 4 weeks later and test the HDAC activity;stained With hematoxylin-eosin(HE)staining and Masson staining of collagen to Observe the lung tissue inflammation and fibrosis,and to measure the lung Tissue hydroxyproline content.Results: Compared to Control Group,the degree of lung inflammation and fibrosis were aggravated after LPS challenge,with increased hydroxyproline Content and increased HDAC activity,which could be delayed by butyric acid precondition.Conclusion: LPS-induced pulmonary fibrosis was relevant to activation of HDAC.Butyric acid,inhibitor of HDAC,could inhibit LPS-induced pulmonary fibrosis by delaying the activation of HDAC.Part two Mechanism of action of histone deacetylase inhibitor on delaying Lipopolysaccharide-induced Pulmonary FibrosisObjective: To determine the mechanism of how butyric acid,inhibitor of HDAC,delay LPS-induced pulmonary fibrosis.Methods: Mice were randomly divided into 3 groups: LPS stimulation group and butyric acid pretreatment + LPS stimulation group and control group.We also take the lung tissue 2 weeks and 4 weeks later and test the Acetylated-histone H3(Ace-H3),Acetylated-histone H4(Ace-H4),thymocyte differentiation antigen-1(Thy-1)and the expression of Thy-1m RNAResults: Compared with the control group,acetylation of lung histone H3,H4 was reduced after intraperitoneal injection of LPS,Thy-1 gene and protein expression was reduced.Butyric acid can delay the process.Conclusion: LPS-induced lung fibrosis is associated with histone H3,H4 deacetylation and inhibition of Thy-1 gene expression.Butyric acid,inhibitor of HDAC,can inhibit the deacetylation of histone H4,thereby delaying the LPS-induced gene expression of Thy-1 and the pulmonary fibrosis.