The histone deacetylase inhibitor trichostatin A has protective effects on acute lung injury in rats after extracorporeal circulation surgery
Objective To investigate the effect and mechanism of Trichostatin A(TSA)on pulmonary injury during cardiopulmonary bypass in rats.Methods Thirty adult male SD rats were randomly divided into Sham group,CPB lung injury group(I/R group),CPB lung injury+TSA 50 ng/kg group(TSA1 group),CPB lung injury+TSA 100 ng/kg group(TSA2 group),and CPB lung injury+TSA 150 ng/kg group(TSA3 group),with 6 animals in each group.The Sham group only underwent vascular puncture and catheterization,while the I/R group and TSA group were established as CPB models.The TSA group also received Trichostatin A before the experiment.The oxygenation index(OI)and respiratory index(RI)were calculated,and the morphological and pathological changes of the left lung were observed after HE staining.The inflammatory factors in lung tissue ho-mogenate and BALF were measured by ELISA,and the expression of HDAC2,AC-H3 and NF-kB P65 was detec-ted by WB.Results The lung function index OI showed that the TSA group was higher than the I/R group at T2 and T3,and the TSA3 group was the highest in the TSA group,while the RI was the opposite(P<0.05).The pathological injury score showed that the TSA group was lower than the I/R group,and the TSA3 group was the lowest in the TSA group(P<0.05).The content of TNF-α and IL-1βin lung tissue homogenates and the con-tent of TNF-α and total protein in BALF showed that the TSA group was lower than the I/R group,and the TSA3 group was the lowest in the TSA group(P<0.05).The expression of HDAC2 in lung tissue showed that the TSA group was lower than the I/R group,and the TSA3 group was the lowest in the TSA group,while the expression of AC-H3 was the opposite(P<0.05).The expression of NF-κBp65 in nucleus showed that the TSA group was lower than the I/R group,and the TSA3 group was the lowest in the TSA group,while the expression in the cyto-plasm was the opposite(P<0.05).Conclusion TSA can reduce lung injury during cardiopulmonary bypass in rats in a concentration-dependent manner,possibly by increasing histone acetylation and decreasing the expres-sion of NF-κB p65 in the nucleus,thereby reducing lung inflammation.
国家科技期刊平台
NSTL
万方数据
