组蛋白去乙酰化酶抑制剂曲古霉素A对大鼠体外循环术后急性肺损伤的保护作用  

The histone deacetylase inhibitor trichostatin A has protective effects on acute lung injury in rats after extracorporeal circulation surgery

作　　者：代树丽 王波 王勇 唐金清 朱文霞 张红 Dai Shuli;Wang Bo;Wang Yong;Tang Jinqing;Zhu Wenxia;Zhang Hong(Department of Anesthesiology,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563000,China;Department of Anesthesiology,The Third Affiliated Hospital of Zunyi University,Zunyi Guizhou 563000,China)

机构地区：[1]遵义医科大学附属医院麻醉科,贵州遵义563000 [2]遵义医科大学第三附属医院麻醉科,贵州遵义563000

出　　处：《遵义医科大学学报》2024年第7期673-682,共10页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:8206020431)。

摘　　要：目的探究曲古霉素A(TSA)对大鼠体外循环肺损伤的影响及作用机制。方法将30只成年雄性SD大鼠随机分为假手术组(Sham组)、CPB肺损伤组(I/R组)、CPB肺损伤+TSA给药50 ng/kg组(TSA1组)、CPB肺损伤+TSA给药100 ng/kg组(TSA2组)、CPB肺损伤+TSA给药150 ng/kg组(TSA3组),每组各6只。Sham组仅行血管穿刺置管,I/R组和TSA组构建CPB模型,TSA组还需术前使用曲古霉素A。体外循环前(T1)、开放肺门后10 min(T2)和实验结束时(T3)查血气,计算氧合指数(OI)、呼吸指数(RI)。取左肺组织HE染色后观察形态和病理损伤评分,ELISA法测肺组织匀浆和肺泡灌洗液中炎症因子含量,WB法测HDAC2、AC-H3及NF-kB P65表达。结果肺功能指标OI在T2、T3时刻表现为TSA组高于I/R组,TSA组中TSA3组最高,RI与之相反(P<0.05);病理损伤评分表现为TSA组低于I/R组、TSA组中TSA3组最低(P<0.05);肺组织匀浆中TNF-α、IL-1β含量以及BALF中TNF-α、总蛋白含量均表现为TSA组低于I/R组、TSA组中TSA3组最低(P<0.05);肺组织中HDAC2表达表现为TSA组低于I/R组、TSA组中TSA3组最低,AC-H3的表达与之相反(P<0.05);NF-κBp65在胞核内表现为TSA组低于I/R组、TSA组中TSA3组最低,胞质内与之相反(P<0.05)。结论TSA可减轻大鼠体外循环肺损伤,且存在浓度依赖性,其机制可能是增加了组蛋白乙酰化,降低NF-κBp65在细胞核内的表达,从而减轻肺部炎症反应。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 homogenate and BALF were measured by ELISA,and the expression of HDAC2,AC-H3 and NF-kB P65 was detected 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-αand IL-1βin lung tissue homogenates and the content of TNF-αand 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 cytoplasm 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

关 键 词：曲古霉素A 体外循环 肺损伤 

分 类 号：R614.2[医药卫生—麻醉学]