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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英文版,2025,45(3):409-416.[Click to copy
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| 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 |
| 戴晖,刘佳丽,刘巧玲,李昕染,卞聪慧,钱海华,张丹 |
| (南京中医药大学附属医院, 江苏 南京 210029) |
| 摘要: |
| 目的 探讨养阴生肌散通过腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白（AMPK/mTOR）信号通路调控自噬改善克罗恩病大鼠肠纤维化的作用机制。方法 将28只大鼠随机分为对照组、模型组、美沙拉嗪组（420 mg/kg）、养阴生肌散组（100 mg/kg），每组7只。参考Morris方法制备克罗恩病肠纤维化模型，药物组均灌肠0.5 mL，1次/d，共4周。观察大鼠的一般情况，计算疾病活动指数（DAI）评分；对结肠组织进行HE染色并行结肠黏膜损伤指数（CMDI）评分、组织学病变评分，进行Masson染色并行纤维化指数评分；采用Western blot法检测AMPK、mTOR、核糖体蛋白S6激酶（p70S6K）、真核翻译起始因子4E结合蛋白1（4EBP1）、微管相关蛋白1轻链3（LC3）蛋白水平；运用RT-PCR法检测肌球蛋白样BCL2结合蛋白（Beclin-1）、螯合体1（P62）的mRNA水平。结果 与对照组比较，模型组体质量下降百分率分数显著上升（P<0.01），DAI评分、CMDI评分、组织学病变评分、纤维化指数评分均显著增高（P<0.01）；LC3Ⅱ/LC3I、p-AMPK/AMPK、p-4EBP1/4EBP1、p-mTOR/mTOR表达量显著降低（P<0.01），p-p70S6K/p70S6K显著增高（P<0.01）；Beclin-1表达量明显降低（P<0.01），P62表达量明显增高（P<0.01）。与模型组比较，美沙拉嗪组和养阴生肌散组体质量下降百分率分数均显著升高（P<0.01），DAI评分、CMDI评分、组织学病变评分、纤维化指数评分均显著降低（P<0.01）；LC3Ⅱ/LC3I、p-AMPK/AMPK、p-4EBP1/4EBP1、p-mTOR/mTOR表达量显著升高（P<0.01），p-p70S6K/p70S6K显著降低（P<0.01）；Beclin-1表达量明显上升（P<0.05），P62表达量明显下降（P<0.01）。结论 养阴生肌散可能通过AMPK/mTOR通路介导的自噬激活改善克罗恩病肠纤维化。 |
| 关键词: 克罗恩病 肠纤维化 养阴生肌散 自噬 AMPK/mTOR信号通路 |
| DOI：10.3969/j.issn.1674-070X.2025.03.003 |
| Received:September 10, 2024 |
| 基金项目:国家自然科学青年基金项目（81904203）。 |
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| The mechanism of action of Yangyin Shengji Powder in alleviating intestinal fibrosis in Crohn disease by regulating autophagy through AMPK/mTOR signaling pathway |
| DAI Hui, LIU Jiali, LIU Qiaoling, LI Xinran, BIAN Conghui, QIAN Haihua, ZHANG Dan |
| (Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China) |
| 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 disease 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. |
| Key words: Crohn disease intestinal fibrosis Yangyin Shengji Powder autophagy AMPK/mTOR signaling pathway |
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