基于HDAC6/NF-κB信号通路探讨莪术提取物治疗慢性萎缩性胃炎的作用机制  

Mechanism of Curcumae Rhizoma Extract in the Treatment of Chronic Atrophic Gastritis Based on HDAC6/NF-κB Signaling Pathway

作　　者：方永乐 李芸 於瑶瑶 FANG Yongle;LI Yun;YU Yaoyao(Dept.of Traditional Chinese Medicine,Huainan East Hospital Group,Anhui Huainan 232000,China)

机构地区：[1]淮南东方医院集团总院中医科,安徽淮南232000

出　　处：《中国医院用药评价与分析》2024年第10期1217-1220,共4页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：安徽省卫生厅医药科研计划项目(No.13167KJ20200122)。

摘　　要：目的:探讨莪术提取物治疗慢性萎缩性胃炎(CAG)的作用机制。方法:选取成年雄性C57BL6/J小鼠,通过1-甲基-3-硝基-1-亚硝基胍构建CAG小鼠模型,采用莪术提取物对模型小鼠灌胃处理。采用定量反转录聚合酶链反应(qRT-PCR)、蛋白质印迹法检测组蛋白去乙酰化酶6(HDAC6)表达;采用苏木精-伊红染色观察胃组织病理学变化;采用酶联免疫吸附试验检测胃泌素17(G-17)、白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)的含量;采用蛋白质印迹法检测核因子κB(NF-κB)信号通路关键蛋白p65的磷酸化及乙酰化,NF-κB抑制因子α(IκBα)的磷酸化;采用免疫共沉淀检测HDAC6与p65的结合。结果:CAG小鼠胃组织中HDAC6呈低表达,HDAC6可与p65特异性结合。CAG小鼠胃组织细胞形态及排列紊乱,G-17、IL-8和TNF-α含量升高,p65蛋白磷酸化、乙酰化增加,IκBα磷酸化减少;而莪术提取物处理后,HDAC6的表达显著上调,小鼠胃组织细胞形态恢复、结构排列完整,G-17、IL-8和TNF-α含量降低,p65蛋白磷酸化、乙酰化减少,IκBα磷酸化增加。结论:莪术提取物可能通过上调HDAC6促进p65的去乙酰化,从而抑制NF-κB信号通路激活,最终改善CAG。OBJECTIVE:To explore the mechanism of Curcumae rhizoma extract in the treatment of chronic atrophic gastritis(CAG).METHODS:Mature male C57BL6/J mice were extracted to construct CAG mice model with 1-methyl-3-nitro-1-nitroguanidine,and the mice model were administrated with Curcumae rhizoma extract by gavage.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting were used to detect histone deacetylase 6(HDAC6)expression.Hematoxylin-Eosin staining was used to observe histopathologic changes in the gastric tissues.Levels of gastrin 17(G-17),interleukin 8(IL-8)and tumor necrosis factorα(TNF-α)were detected by enzyme-linked immunosorbent assay.Phosphorylation and acetylation of p65,a key protein in the nuclear factorκB(NF-κB)signaling pathway,and phosphorylation of NF-κB inhibitory factorα(IκBα)were detected by Western blotting.The combination of HDAC6 and p65 was detected by co-immunoprecipitation.RESULTS:HDAC6 was lowly expressed in the gastric tissues of CAG mice,and HDAC6 could bind specifically to p65.The morphology and arrangement of gastric cells in CAG mice were disordered,the levels of G-17,IL-8,TNF-α,the phosphorylation and acetylation of p65 protein increased,and the phosphorylation of IκBαdecreased.After treatment of Curcumae rhizoma extract,the expression of HDAC6 was significantly up-regulated,the morphology and the morphology and structure of the cells in the mouse stomach tissue were restored and arranged in a complete manner,the levels of G-17,IL-8,TNF-α,the phosphorylation and acetylation of p65 protein decreased,and the phosphorylation of IκBαincreased.CONCLUSIONS:Curcumae rhizoma extract may promote the deacetylation of p65 through up-regulating HDAC6 expression,thereby inhibiting NF-κB signaling pathway activation and ultimately improving CAG.

关 键 词：慢性萎缩性胃炎 莪术提取物 组蛋白去乙酰化酶6 核因子ΚB 乙酰化 磷酸化 

分 类 号：R932[医药卫生—生药学] R965[医药卫生—药学]