Protective effects of histone deacetylase inhibitors trichostatin A on acute lung injury in septic mice / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects of histone deacetylase inhibitors trichostatin A (TSA) on acute lung injury in septic mice.Methods Septic mice model was induced by cecal ligation and puncture(CLP).Ninty male BALB/c mice of clean grade were randomly(random number) divided into six groups(n=15),namely sham operation group,CLP group,CLP+DMSO group,CLP+TSA 1 mg group,CLP+TSA 5 mg group,and CLP+TSA 10 mg group.TSA(1 mg/kg,5 mg/kg,10 mg/kg) was administrated 12 hours before operation by intraperitoneal injection.And mice in sham group were only treated with laparotomy without CLP,and 24 h later,all survived mice were sacrificed to obtain specimens.ELISA method was employed to detect the concentrations of TNF-α and IL-1β in BALF.The lung wet/dry ratio was calculated.Histopathology changes of lung tissues were observed under light microscope.Lung tissue cell apoptosis was detected by TUNEL method.Caspase-3,Caspase-9 and CytC were assayed by Western blotting.The survival rate of mice in each group was calculated by additional 120 mice.Data were analyzed by SPSS 23.0.Statistical analyses were performed using independent sample t-test to compare between two groups or one-way analysis of variance test to compare among muhiple groups.The survival rate of mice was analyzed by univariate analysis using log-rank test.Results The lung W/D(P=0.021),the concentrations of TNF-α(P=0.000 1)and IL-1β(P=0.000 6)in BALF,puhnonary pathological change(P=0.001 6),lung tissue cell apoptotic index(P=0.000 9),the levels of apoptosis proteins (P＜0.05) in CLP group were higher than those in sham group,while survival rate (P=0.000 1) in CLP groups was lower than that in sham group.Compared with DMSO,the TSA significantly reduced the lung W/D,the levels of TNF-α.IL-1β in BALF,pathologic changes of lung tissue,lung tissue cell apoptotic index and the levels of apoptosis proteins in septic mice(P＜0.05).The increase in survival rate (P=0.007 2) associated with TSA(10 mg/kg)administration.Conclusion TSA exerts protective effects through attenuating pro-inflammatory cytokines and lung tissue cell apoptosis in sepsis induced acute lung injury in mice.