基础医学与临床2025，Vol.45Issue(10)：1326-1332,7.DOI:10.16352/j.issn.1001-6325.2025.10.1326
白术内酯Ⅰ减轻葡聚糖硫酸钠诱导的慢性结肠炎模型大鼠的炎性反应
Atractylenolide Ⅰ mitigates the inflammatory response in a rat model of dextransulfate sodium-induced chronic colitis
摘要
Abstract
Objective To investigate the effect of Atractylenolide Ⅰ(AtraⅠ)on chronic colitis rats by regulation of cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response binding protein(CREB)pathway.Methods Rats were randomly divided into control group,chronic colitis model group[model,free feeding with 2%dextran sulfate sodium(DSS)followed by 7 days of conventional drinking water alternatively for 42 days],AtraⅠ low(AtraⅠ-L,8.33 mg/kg AtraⅠ)and high(AtraⅠ-H,33.32 mg/kg AtraⅠ)intervention model group,positive drug(mesalazine)group(150 mg/kg mesalazine)and high concentration of AtraⅠ+cAMP inhibitor(SQ22536)group(33.32 mg/kg AtraⅠ+2.13 mg/kg SQ22536),18 rats in each group.Disease activi-ty index(DAI)and colon length were measured.HE staining was applied to detect pathological changes in colon tissue.Immunohistochemical staining was applied to detect the expression of zonula occluden-1(ZO-1)and mucin 2(MUC2)in colon tissue.ELISA was applied to detect level of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10 and cAMP in colon tissue.Western blot was applied to detect p-PKA and p-CREB proteins in colon tissue.Results Compared with the control group,the colon wall of the model group was edema and thickened,the number of inflammatory cell infiltration was increased,the colon length was shortened.DAI score and TNF-α and IL-6 level in the colon tissue were increased.The positive expression of MUC2 and ZO-1,the level of IL-10 and the protein of cAMP,p-PKA and p-CREB in colon tissues were decreased(P＜0.05).Compared with model group,the pathological damage of colon tissue in AtraⅠ-L group,AtraⅠ-H group,and mesalazine group was alleviated,the colon length increased,the DAI score reduced,level of TNF-α and IL-6 in colon tissue reduced and the posi-tive expression of MUC2 and ZO-1,level of IL-10,and cAMP,p-PKA,and p-CREB proteins in colon tissue were all elevated(P＜0.05).SQ22536 attenuated the improvement effect of AtraⅠ-H on intestinal mucosal barrier func-tion and the inhibitory effect on inflammatory response in rats with chronic colitis.Conclusions AtraⅠ improves intestinal mucosal barrier function and inhibits inflammation in rats with chronic colitis,and its mechanism may be related to the upregulation of the cAMP/PKA/CREB pathway.关键词
白术内酯Ⅰ/环磷酸腺苷/蛋白激酶A/cAMP反应元件结合蛋白通路/慢性结肠炎/炎性反应/肠黏膜屏障Key words
atractylenolide Ⅰ/cyclic adenosine monophosphate/protein kinase A/cyclic-AMP response element binding protein path-way/chronic colitis/inflammation/intestinal mucosal barrier分类
医药卫生引用本文复制引用
牟忠颜,刘志敏,朱曙光..白术内酯Ⅰ减轻葡聚糖硫酸钠诱导的慢性结肠炎模型大鼠的炎性反应[J].基础医学与临床,2025,45(10):1326-1332,7.基金项目
烟台市科技计划项目(2021YD076) （2021YD076）
