祛湿活血方通过AMPK/mTOR/ULK1自噬信号通路改善代谢相关脂肪性肝病的作用机制研究 点击下载
论文标题： 祛湿活血方通过AMPK/mTOR/ULK1自噬信号通路改善代谢相关脂肪性肝病的作用机制研究
英文标题：
中文摘要： 目的 基于AMP活化蛋白激酶/哺乳动物雷帕霉素靶蛋白/UNC-51样激酶1（AMPK/mTOR/ULK1）自噬信号通路，探讨祛湿活血方改善代谢相关脂肪性肝病（MAFLD）的作用机制。方法取雄性C57BL/6J小鼠，分为正常组、模型组和祛湿活血方低、中、高剂量组[4.10、8.20、16.40mg/（g·d）]，每组10只。除正常组外，其余各组小鼠采用高脂饲料喂养12周建立MAFLD模型。造模完成后24h开始，各组小鼠每日给予相应药液或生理盐水干预，每日1次，持续干预6周。按照试剂盒说明书检测血清总胆固醇（TC）、甘油三酯（TG）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平；采用HE染色、油红O染色观察小鼠肝组织病理变化；采用Westernblot、免疫荧光染色法检测小鼠AMPK/mTOR/ULK1自噬信号通路相关蛋白表达及蛋白阳性表达情况。结果与正常组相比，模型组小鼠血清TC、TG、ALT、AST及LDL-C水平均显著升高，HDL-C水平显著下降（P＜0.01）；HE染色可见模型组肝细胞出现明显脂肪变性，油红O染色显示小鼠肝组织内有大量脂滴堆积；Westernblot和免疫荧光染色结果显示，模型组小鼠肝组织中p-mTOR/mTOR、p62蛋白表达水平以及p-mTOR、p62蛋白的相对荧光强度均显著升高/增强（P＜0.01），p-AMPK/AMPK、ULK1、微管相关蛋白1轻链3Ⅱ（LC3Ⅱ）蛋白表达水平以及p-AMPK、LC3蛋白的相对荧光强度均显著降低/减弱（P＜0.01）。经祛湿活血方干预后，祛湿活血方低、中、高剂量组小鼠上述肝组织病理改变和异常指标均得到显著逆转，大部分指标差异有统计学意义（P＜0.05或P＜0.01）。结论祛湿活血方可显著改善MAFLD模型小鼠的肝脏病理形态、血脂水平与肝功能，该改善作用可能通过激活AMPK/mTOR/ULK1自噬信号通路实现。
英文摘要： OBJECTIVE To investigate the mechanism of Qushi huoxue decoction in improving metabolic-associated fatty liver disease （MAFLD） based on the AMP-activated protein kinase/mammalian target of rapamycin/UNC-51-like kinase 1 （AMPK/mTOR/ULK1） autophagy signaling pathway.METHODS Male C57BL/6J mice were randomly divided into normal group， model group， and low-， medium-， and high-dose Qushi huoxue decoction groups [4.10， 8.20， 16.40 mg/（g·d）]， with 10 mice in each group. Except for the normal group， mice in the other groups were fed a high-fat diet for 12 weeks to establish the MAFLD model. Starting 24 hours after modeling， mice in each group were administered the drug solution or normal saline once daily for 6 consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， alanine transaminase （ALT）， aspartate transferase （AST）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected according to the kit instructions. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe pathological changes in mouse liver tissue. Western blot and immunofluorescence staining were used to detect the expression and positive protein expression related to the AMPK/mTOR/ULK1 autophagy signaling pathway.RESULTS Compared with the normal group， the serum levels of TC， TG， ALT， AST， and LDL-C in the model group were significantly increased， while the HDL-C level was significantly decreased （ P ＜0.01）. HE staining showed obvious steatosis in hepatocytes of the model group， and oil red O staining showed a large amount of lipid droplet accumulation in liver tissue. Western blot and immunofluorescence staining results showed that the expression levels of p-mTOR/mTOR and p62 proteins， as well as the relative fluorescence intensities of p-mTOR and p62 proteins in liver tissue of the model group， were significantly increased/enhanced （ P ＜0.01）， while the expression levels of p-AMPK/AMPK， ULK1， and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） proteins， as well as the relative fluorescence intensities of p-AMPK and LC3 proteins， were significantly decreased/weakened （ P ＜0.01）. After intervention with Qushi huoxue decoction， the above pathological changes and abnormal indicators in liver tissue of mice in the low-， medium-， and high-dose groups were significantly reversed， with most indicators showing statistically significant differences （ P ＜0.05 or P ＜0.01）.CONCLUSIONS Qushi huoxue decoction can significantly improve liver pathology， blood lipid levels， and liver function in MAFLD model mice； this improvement may be achieved through the activation of the AMPK/mTOR/ULK1 autophagy signaling pathway.
期刊： 2026年第37卷第16期
作者： 龚晓倩；谭伟强；魏业煌；王蓉蓉；唐艳芳；刘旭东
英文作者： GONG Xiaoqian，TAN Weiqiang，WEI Yehuang，WANG Rongrong，TANG Yanfang，LIU Xudong
关键字： 祛湿活血方；代谢相关脂肪性肝病；AMPK/mTOR/ULK1；自噬
KEYWORDS： Qushi huoxue decoction;metabolic associated fatty liver disease;AMPK/mTOR/ULK1;Autophagy
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