湖南中医药大学学报2025，Vol.45Issue(3)：409-416,8.DOI:10.3969/j.issn.1674-070X.2025.03.003
养阴生肌散通过AMPK/mTOR信号通路调控自噬改善克罗恩病肠纤维化的作用机制研究
The mechanism of action of Yangyin Shengji Powder in alleviating intestinal fibrosis in Crohn disease by regulating autophagy through AMPK/mTOR signaling pathway
摘要
Abstract
Objective To explore the mechanism of action of Yangyin Shengji Powder(YYSJP)in alleviating intestinal fibrosis in rats with Crohn disease by regulating autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)signaling pathway.Methods A total of 28 rats were randomly divided into control group,model group,mesalazine group(420 mg/kg),and YYSJP group(100 mg/kg),with 7 rats in each group.The intestinal fibrosis model of Crohn disease was prepared according to the Morris method.The drug group was given enema of 0.5 mL once a day for a total of four weeks.The general condition of rats was observed,and the disea se activity index(DAI)was calculated;HE staining on colon tissue was performed to evaluate the colonic mucosa damage index(CMDI)and histological lesion score.Masson staining was used to evaluate the fibrosis index;Western blot was applied to measure the protein levels of AMPK,mTOR,ribosomal protein S6 kinase(p70S6K),eukaryotic translation initiation factor 4E-binding protein 1(4EBP1),and microtubule-associated protein 1 light chain 3(LC3).RT-PCR was employed to measure the mRNA levels of Beclin-1 and sequestosome 1(P62).Results Compared with the control group,the body weight loss percentage in the model group significantly elevated(P<0.01),DAI score,CMDI score,histological lesion score,and fibrosis index score all significantly increased(P<0.01);LC3Ⅱ/LC3I,p-AMPK/AMPK,p-4EBP1/4EBP1,and p-mTOR/mTOR expression levels significantly decreased(P<0.01),while p-p70S6K/p70S6K significantly increased(P<0.01);Beclin-1 expression level significantly decreased(P<0.01),and P62 expression level significantly increased(P<0.01).Compared with the model group,the body weight loss percentage of the mesalazine group and YYSJP group both significantly increased(P<0.01).DAI score,CMDI score,histological lesion score,and fibrosis index score all significantly decreased(P<0.01);the expression levels of LC3Ⅱ/LC3I,p-AMPK/AMPK,p-4EBP1/4EBP1,and p-mTOR/mTOR all significantly increased(P<0.01),while p-p70S6K/p70S6K significantly decreased(P<0.01);Beclin-1 expression level significantly increased(P<0.05),and P62 expression level significantly decreased(P<0.01).Conclusion YYSJP may alleviate intestinal fibrosis in Crohn disease by regulating autophagy through AMPK/mTOR signaling pathway.关键词
克罗恩病/肠纤维化/养阴生肌散/自噬/AMPK/mTOR信号通路Key words
Crohn disease/intestinal fibrosis/Yangyin Shengji Powder/autophagy/AMPK/mTOR signaling pathway分类
医药卫生引用本文复制引用
戴晖,刘佳丽,刘巧玲,李昕染,卞聪慧,钱海华,张丹..养阴生肌散通过AMPK/mTOR信号通路调控自噬改善克罗恩病肠纤维化的作用机制研究[J].湖南中医药大学学报,2025,45(3):409-416,8.基金项目
国家自然科学青年基金项目(81904203). （81904203）
