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薛小嫣, 黎鹏程, 尹抗抗.降脂理肝汤抑制铁死亡改善非酒精性脂肪性肝病小鼠的研究[J].湖南中医药大学学报英文版,2025,45(3):432-437.[Click to copy
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降脂理肝汤抑制铁死亡改善非酒精性脂肪性肝病小鼠的研究 |
薛小嫣,黎鹏程,尹抗抗 |
(湖南中医药大学中医学院, 湖南 长沙 410006;湖南中医药大学资产与实验室管理处, 湖南 长沙 410006) |
摘要: |
目的 研究降脂理肝汤对非酒精性脂肪性肝病(NAFLD)小鼠的影响,并探究其中的作用机制。方法 将60只SPF级C57BL/6小鼠随机分成空白组、模型组、铁死亡抑制剂组(1 mg·kg-1)和降脂理肝汤高、中、低剂量组(13.30、6.60、3.30 g·kg-1)。通过喂养12周高脂饲料(HFD)建立NAFLD模型。造模成功后,每组每天分别给对应的药物,连续6周。本实验检测小鼠血清中游离脂肪酸(FFA)、甘油三酯(TG)、天门冬氨酸氨基转移酶(AST)以及丙氨酸氨基转移酶(alanine aminotransferase, ALT)的含量;采用油红O染色法和HE染色法检测肝脏脂质沉积和病理损伤情况;通过RT-qPCR检测肝组织中核因子E2相关因子2(Nrf2)、胱氨酸谷氨酸转运蛋白(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)的mRNA表达情况;通过Western blot检测肝组织中Nrf2、SLC7A11以及GPX4的蛋白表达情况。结果 与空白组相比,模型组小鼠肝脏重量和肝脏指数上升(P<0.05),肝功能ALT、AST指标上升(P<0.01,P<0.05),肝脏有明显的脂肪变性,肝小叶结构紊乱,Nrf2、SLC7A11和GPX4蛋白及mRNA表达显著下降(P<0.01)。与模型组相比,铁死亡抑制剂组小鼠肝脏重量和肝脏指数下降(P<0.05,P<0.01),肝小叶结构清晰,血清中ALT、AST和TG含量下降(P<0.01,P<0.05),Nrf2、SLC7A11和GPX4 蛋白及mRNA表达上升(P<0.01)。高剂量降脂理肝汤组小鼠肝脏重量和肝脏指数下降(P<0.05),肝功能显著改善,血脂FFA、TG下降(P<0.05,P<0.01),Nrf2、SLC7A11和GPX4 蛋白及mRNA的表达水平上调(P<0.05)。降脂理肝汤中、低剂量组小鼠肝脏指数下降(P<0.05,P<0.01),肝功能改善,血清中FFA、TG含量降低(P<0.05,P<0.01)。结论 降脂理肝汤可降低血脂,改善肝功能,减轻NAFLD,这可能与抑制铁死亡相关。 |
关键词: 非酒精性脂肪性肝病 铁死亡 降脂理肝汤 Nrf2 SLC7A11 GPX4 |
DOI:10.3969/j.issn.1674-070X.2025.03.006 |
Received:December 27, 2024 |
基金项目:湖南省自然科学基金面上项目(2022JJ30446);湖南省教育厅优秀青年基金项目(21B0393)。 |
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Study on Jiangzhi Ligan Decoction inhibiting ferroptosis and alleviating non-alcoholic fatty liver disease in mice |
XUE Xiaoyan, LI Pengcheng, YIN Kangkang |
(School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410006, China;Office of Asset & Laboratory Management, Hunan University of Chinese Medicine, Changsha, Hunan 410006, China) |
Abstract: |
Objective To investigate the effects of Jiangzhi Ligan Decoction (JZLGD) on non-alcoholic fatty liver disease (NAFLD) mice and explore its mechanism of action. Methods Sixty SPF-grade C57BL/6 mice were randomly divided into blank group, model group, ferroptosis inhibitor group (1 mg/kg-1), and high-, medium-, and low-dose JZLGD groups (13.30, 6.60, and 3.30 g/kg-1). The NAFLD model was established by feeding the mice high fat diet (HFD) for 12 weeks. After successful modelling, each group was given the corresponding medication daily for six consecutive weeks. In this experiment, the serum levels of free fatty acids(FFA), triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined in mice, the hepatic lipid deposition and pathological damage in liver tissue were examined by Oil Red O staining and HE staining, the mRNA expressions of Nrf2, SLC7A11, and GPX4 in liver tissue were checked by RT-qPCR, and the protein expressions of Nrf2, SLC7A11, and GPX4 in liver tissue were determined by Western blot. Results Compared with mice in the blank group, the mice in the model group exhibited increased liver weight and liver index (P<0.05), elevated liver function indicators ALT and AST (P<0.01, P<0.05), obvious steatosis in the liver, disordered hepatic lobule structure, and significantly reduced protein and mRNA expressions of Nrf2, SLC7A11, and GPX4 (P<0.01). Compared with the model group, mice in the ferroptosis inhibitor group showed decreased liver weight and liver index (P<0.05, P<0.01), clear liver lobule structure, reduced serum levels of ALT, AST, and TG (P<0.01, P<0.05), and increased protein and mRNA expressions of Nrf2, SLC7A11, and GPX4 (P<0.01). Mice in the high-dose JZLGD group showed decreased liver weight and liver index (P<0.05), significantly improved liver function, reduced blood lipids (TG and FFA) (P<0.05, P<0.01), and upregulated protein and mRNA expressions of Nrf2, SLC7A11, and GPX4 (P<0.05). Mice in the medium- and low-dose JZLGD groups also showed decreased liver index (P<0.05, P<0.01), improved liver function, and reduced serum levels of FFA and TG (P<0.05, P<0.01). Conclusion JZLGD can reduce blood lipids, improve liver function, and alleviate NAFLD, potentially through inhibiting ferroptosis. |
Key words: non-alcoholic fatty liver disease ferroptosis Jiangzhi Ligan Decoction Nrf2 SLC7A11 GPX4 |
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