小青龙汤通过调节细胞外组蛋白HATs/HDACs平衡减轻脓毒症所致急性呼吸窘迫综合征  

Xiao-Qing-Long-Tang Attenuates Sepsis-induced Acute Respiratory Distress Syndrome via Regulating Extracellular Histone Acetyltransferases/Histone Deacetylases Balance

作　　者：杨洞洞 张青 蒋镥[1] YANG Dongdong;ZHANG Qing;JIANG Lu(The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,China)

机构地区：[1]浙江中医药大学附属第一医院(浙江省中医院),杭州310006

出　　处：《中国现代应用药学》2025年第3期333-340,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(82104763);浙江省中医药科技计划项目(2020ZB070)。

摘　　要：目的探讨小青龙汤(Xiao-Qing-Long-Tang,XQLT)在治疗脓毒症诱导的急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)小鼠中的具体作用机制。方法采用盲肠结扎和穿孔(cecal ligation and puncture,CLP)建立BALB/c小鼠脓毒症模型。试剂盒检测组蛋白乙酰转移酶(histone acetyltransferase,HAT)和组蛋白去乙酰化酶(histone deacetylase,HDAC)活性。Western blotting分析小鼠肺组织中乙酰组蛋白H3、凋亡相关蛋白、HDAC2、HDAC7和HDAC8的表达。ELISA检测脓毒症相关细胞因子的浓度。qRT-PCR确定小鼠血液中脓毒症相关细胞因子的水平、小鼠肺组织中HDAC的表达和凋亡相关蛋白的表达。HE染色观察肺组织切片病理状况。结果XQLT可减弱CLP小鼠中HAT活性和乙酰组蛋白H3含量的下降,促进HDAC活性,抑制脓毒症相关细胞因子浓度,减轻肺损伤和肺细胞凋亡。此外,HDAC2过表达逆转XQLT对乙酰组蛋白H3表达的促进作用及其对肺损伤和肺细胞凋亡的缓解作用。结论XQLT通过调节细胞外HATs/HDACs平衡减轻脓毒症诱导的ARDS。OBJECTIVE To explore the specific action mechanism of Xiao-Qing-Long-Tang(XQLT)in the treatment of mice suffering from sepsis-induced acute respiratory distress syndrome(ARDS).METHODS Sepsis was induced by cecal ligation and puncture(CLP)in BALB/c mice.Histone acetyltransferase(HAT)and histone deacetylase(HDAC)activities were detected by kits respectively.Western blotting was used to analyze acetyl histone H3,apoptosis-related proteins,HDAC2,HDAC7 and HDAC8 expression in lung tissue of mice.The concentrations of sepsis-related cellular factors were examined using ELISA.qRT-PCR identified sepsis-related cellular factor levels in the mouse blood,HDAC expression and apoptosis-related protein expression in mouse lung tissue.Lung tissue sections were stained with HE for the observation of pathological condition.RESULTS XQLT attenuated decline in HAT activity and acetyl histone H3 content,facilitated HDAC activity,suppressed concentration of sepsisrelated cellular factors,alleviated lung injury and lung cell apoptosis in CLP mice.The promotion of XQLT on acetyl histone H3 expression and its mitigative effect on the lung injury as well as lung cell apoptosis were overturned by HDAC2 overexpression.CONCLUSION XQLT attenuated sepsis-induced ARDS via regulating extracellular HATs/HDACs balance.

关 键 词：小青龙汤 脓毒症 急性呼吸窘迫综合征 组蛋白乙酰转移酶 组蛋白去乙酰化酶 

分 类 号：R285.5[医药卫生—中药学]