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基于代谢组学研究柴胡皂苷C对急性肝损伤小鼠的保护作用
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| 篇名： | 基于代谢组学研究柴胡皂苷C对急性肝损伤小鼠的保护作用 |
| TITLE： | Study on the protective effect of saikosaponin C on acute liver injury in mice based on metabolomics |
| 摘要： | 目的 基于血清代谢组学研究柴胡皂苷C（SSC）对四氯化碳（CCl4）诱导的急性肝损伤（ALI）小鼠的保护作用及机制。方法将40只小鼠按随机数字表法分为空白组（水）、模型组（水）、阳性对照药组（联苯双酯滴丸，150mg/kg）和SSC低、高剂量组（2.5、10mg/kg），每组8只，每天灌胃水/药物1次，连续7d。末次给药1h后，除空白组外的其余各组小鼠均腹腔注射0.2%CCl4橄榄油溶液以建立ALI模型。造模17h后，计算小鼠肝指数，检测小鼠血清中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β水平，观察小鼠肝组织病理学变化，并采用液质联用法对小鼠血清进行代谢组学分析。结果与空白组比较，模型组小鼠肝指数和ALT、AST、LDH、TNF-α、IL-6、IL-1β水平均显著升高（P＜0.01）；肝细胞出现水肿、空泡变性并有较多坏死，可见炎症细胞大量浸润。与模型组比较，SSC高剂量组小鼠肝指数和血清指标水平均显著降低（P＜0.05或P＜0.01），且肝组织病理学损伤明显改善。代谢组学研究结果显示，与模型组比较，SSC高剂量组小鼠血清中上调的差异代谢物有63个、下调的有256个（包括前列腺素B2、20-羟基白三烯B4、5-羟色氨酸、7α-羟基胆固醇等代谢物），主要涉及花生四烯酸代谢、5-羟色胺突触、初级胆汁酸生物合成等代谢途径。结论高剂量SSC可通过下调前列腺素B2、20-羟基白三烯B4等关键代谢物水平，减少花生四烯酸代谢、5-羟色胺突触、初级胆汁酸生物合成等代谢途径，进而对CCl4诱导的ALI小鼠发挥保护作用。 |
| ABSTRACT： | OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C （SSC） on acute liver injury （ALI） in mice induced by carbon tetrachloride （CCl4） based on serum metabolomics. METHODS Forty mice were divided into blank group （water）， model group （water）， positive control drug group （Biphenyl diester drop pills， 150 mg/kg）， and SSC low- and high-dose groups （2.5， 10 mg/kg） using the random number table method， with 8 mice in each group. They were given water/ relevant drugs， once a day， for 7 consecutive days. One hour after the last administration， all mice were intraperitoneally injected with 0.2% CCl4 olive oil to induce ALI model， except for the blank group. After 17 hours of the modeling， the liver index of mice was calculated. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in serum of mice were detected. The histopathological changes of liver tissue were observed. Meanwhile， the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry. RESULTS Compared with the blank group， the levels of liver index， ALT， AST， LDH， TNF-α， IL-6， and IL-1β in the model group were significantly increased （P＜0.01）. Hepatocytes were edema， vacuolar degeneration， more necrosis， and a large number of inflammatory cells were infiltrated. Compared with the model group， liver index and serum index levels of mice were significantly decreased （P＜0.05 or P＜0.01）， accompanied by marked improvement in histopathological damage to the liver tissue. The metabolomics results showed that compared with the model group， there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group， including prostaglandin B2， 20-hydroxy-leukotriene B4， 5- hydroxy-L-tryptophan， 7α -hydroxycholesterol， etc.； these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism， 5-hydroxytryptamine synapse， primary bile acid biosynthesis. CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4， and then ruducing metabolic pathways such as arachidonic acid metabolism， 5- hydroxytryptamine synapse， and primary bile acid biosynthesis. |
| 期刊： | 2025年第36卷第05期 |
| 作者： | 李新存；彭东辉；王永福；施亚敏；吴梦娟；付智慧；王娟 |
| AUTHORS： | LI Xincun，PENG Donghui，WANG Yongfu，SHI Yamin，WU Mengjuan，FU Zhihui，WANG Juan |
| 关键字： | 柴胡皂苷C；急性肝损伤；代谢组学；差异代谢物；花生四烯酸代谢；5-羟色胺突触；初级胆汁酸生物合成 |
| KEYWORDS： | saikosaponin C； acute liver injury； metabolomics； differential metabolite； arachidonic acid metabolism； 5-hydroxy- |
| 阅读数： | 1 次 |
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