| 引用本文: |
贺映辉, 高元峰, 陈春茗, 柏玉冰, 欧巧玲, 刘红宇, 唐锋.基于LC-MS非靶向代谢组学技术探讨经典名方化肝煎干预CCl4诱导肝纤维化大鼠的作用机制[J].湖南中医药大学学报,2026,46(2):288-296[点击复制] |
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| 基于LC-MS非靶向代谢组学技术探讨经典名方化肝煎干预CCl4诱导肝纤维化大鼠的作用机制 |
| 贺映辉,高元峰,陈春茗,柏玉冰,欧巧玲,刘红宇,唐锋 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学第二附属医院, 湖南 长沙 410005) |
| 摘要: |
| 目的 基于非靶向代谢组学技术探讨化肝煎干预四氯化碳（CCl4）诱导肝纤维化大鼠的作用机制。方法 以48只适应性喂养1周的SPF级雄性SD大鼠为研究对象，腹腔注射40% CCl4橄榄油溶液诱导肝纤维化大鼠模型。将大鼠按照随机数字表法分为正常组、模型组、化肝煎低剂量组（4.25 g/kg）、化肝煎中剂量组（8.50 g/kg）、化肝煎高剂量组（17.0 g/kg）、阳性组（秋水仙碱，0.2 mg/kg），每组8只。除正常组腹腔注射等体积橄榄油溶液外，其余各组均腹腔注射40% CCl4橄榄油溶液，每周2次，持续8周。从第5周开始，各组分别灌胃给予相应药物或生理盐水，每日1次。实验结束后，麻醉处死大鼠，采集大鼠血清及肝组织，检测大鼠血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST），取肝脏组织进行病理学观察。采用高效液相色谱-质谱联用技术（LC-MS）对大鼠血清进行非靶向代谢组学分析。结果 病理学结果显示，化肝煎中、高剂量组可显著减轻大鼠肝纤维化；与正常组相比，模型组大鼠血清中ALT、AST的含量显著升高（P<0.05）；与模型组比较，化肝煎中、高剂量组AST、ALT的含量显著降低（P<0.05）。代谢组学结果表明，化肝煎组干预后可显著调控磷脂酰胆碱（PC）、磷脂酰乙醇胺（PE）、磷脂酰丝氨酸（PS）、胆酸、去氧胆酸、牛磺胆酸等差异代谢物，其相关代谢途径涉及甘油磷脂代谢、鞘脂信号通路、鞘脂代谢、亚油酸代谢及胆汁分泌等通路。结论 化肝煎可能通过调控甘油磷脂代谢、鞘脂信号通路、鞘脂代谢、亚油酸代谢及胆汁分泌等通路，并降低血清ALT、AST含量，从而达到改善肝纤维化的作用。 |
| 关键词: 化肝煎 肝纤维化 LC-MS技术 代谢组学 甘油磷脂代谢 胆汁分泌 |
| DOI：10.3969/j.issn.1674-070X.2026.02.009 |
| 投稿时间：2025-08-28 |
| 基金项目:国家自然科学基金面上项目(82174069,82474180);湖南省自然科学基金医卫联合项目(2025JJ80962,2025JJ80943);湖南省卫生健康委员会科研计划项目(B202319018491,D202302048806,20256149);湖南省“十四五”中医药学科带头人培养项目(湘中医药[2024]3号);国家中医优势专科建设项目(国中医药医政函[2024]90号)。 |
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| Mechanism of action of the classical formula Huagan Decoction in intervening CCl4-induced hepatic fibrosis in rats based on LC-MS non-targeted metabolomics |
| HE Yinghui, GAO Yuanfeng, CHEN Chunming, BAI Yubing, OU Qiaoling, LIU Hongyu, TANG Feng |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China) |
| Abstract: |
| Objective To investigate the mechanism of action of Huagan Decoction in intervening carbon tetrachloride (CCl4)-induced hepatic fibrosis (HF) in rats based on non-targeted metabolomics. Methods Totally 48 SPF-grade male SD rats were assingned into 6 groups (n=8 per group) using a random number table:normal group, model group, low-(4.25 g/kg), medium-(8.50 g/kg), and high-dose Huagan Decoction groups (17.0 g/kg), and positive group (colchicine, 0.2 mg/kg). Except for the normal group, which received an equal volume of olive oil solution intraperitoneally, all other groups were injected intraperitoneally with 40% CCl4-olive oil solution twice a week for 8 consecutive weeks. From the fifth week onward, each group was given the corresponding drug intervention or saline at the set dose by gavage once daily. At the end of the experiment, the rats were anesthetized and euthanized, whose serum and liver tissue were collected to determine the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the pathological changes were observed. Non-targeted metabolomic analysis of rat serum was performed using liquid chromatography-mass spectrometry (LC-MS). Results Pathological findings showed that medium- and high-dose Huagan Decoction groups significantly alleviated HF in rats. Compared with the normal group, serum ALT and AST levels in the model group were significantly higher (P<0.05); Compared with the model group, AST and ALT activities medium- and high-dose Huagan Decoction groups were significantly reduced (P<0.05). Metabolomics results indicated that Huagan Decoction intervention significantly regulated differential metabolites such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), cholic acid, deoxycholic acid, and taurocholic acid. The related metabolic pathways involved glycerophospholipid metabolism, sphingolipid signaling, sphingolipid metabolism, linoleic acid metabolism, bile secretion, and so on. Conclusion Huagan Decoction can alleviate HF, which may be achieved by regulating pathways such as glycerophospholipid metabolism, sphingolipid signaling, sphingolipid metabolism, linoleic acid metabolism, and bile secretion, as well as by reducing serum levels of ALT and AST. |
| Key words: Huagan Decoction hepatic fibrosis LC-MS technology metabolomics glycerophospholipid metabolism bile secretion |
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