南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (2): 244-251.doi: 10.12122/j.issn.1673-4254.2024.02.06

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竹节参总皂苷缓解CCl4诱导的大鼠急性肝损伤：基于调控PI3K/Akt/NF-κB信号通路

吴广阳，宋添力，唐 浪，王一民，刘 绪，黄 胜   

  1. 湖北民族大学医学部，风湿性疾病发生与干预实验室，湖北 恩施 445000；湖北恩施学院，湖北 恩施 445000
  • 发布日期:2024-03-14

Total saponins of Panax japonicus alleviates CCl4-induced acute liver injury in rats by regulating the PI3K/AktNF-κB signaling pathway

WU Guangyang, SONG Tianli, TANG Lang, WANG Yiming, LIU Xu, HUANG Sheng   

  1. Department of Medicine, Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic diseases, Hubei Minzu University, Enshi 445000, China; Hubei Enshi College, Enshi 445000, China
  • Published:2024-03-14

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摘要： 目的 探讨土家族药用植物竹节参提取物总皂苷对CCl4致急性肝损伤的保护作用及潜在的药理学机制。方法 将6周龄SPF级雄性SD大鼠随机分为正常组、模型组、联苯双酯组（100 mg/kg）、竹节参总皂苷低、中、高（50、100、200 mg/kg）剂量组，各组8只，除空白组外，其余各组采用CCl4诱导大鼠急性肝损伤模型，处理组于造模中给予药物灌胃干预。比较各组大鼠的血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（TBil）和碱性磷酸酶（ALP）水平；HE染色观察肝组织病理学改变；免疫组化检测肝脏组织PI3K/Akt/NF-κB信号通路相关分子的表达；酶联免疫法测定肝脏组织总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）水平；蛋白免疫印迹法检测肝脏组织PI3K-Akt和SIRT6-NF-κB通路相关蛋白表达情况。 结果 网络药理学分析显示，竹节参总皂苷对急性肝损伤的有治疗作用，其关键的通路为PI3K/Akt等信号通路。血清学和酶联免疫学实验结果显示，与正常组相比，模型组大鼠血清和肝组织的AST、ALT、ALP、TBil和MDA明显增高（P<0.01），T-SOD和GSH-Px水平显著降低（P<0.01）；与模型组相比，各治疗组ALT、AST、ALP、TBIL和MDA水平显著降低（P<0.01），T-SOD和GSH-Px水平显著升高（P<0.01）。免疫组化结果显示，正常组大鼠肝组织细胞内未见p-NF-κB表达阳性，与正常组相比，模型组中p-NF-κB阳性表达则明显增加，阳性细胞数增多（P<0.01）；与模型组比较，各治疗组阳性表达明显减少（P<0.01）。免疫印迹结果显示，相对于正常组，模型组PI3K、p-Akt蛋白的表达水平下降，p-NF-κB、TNF-α和IL-6蛋白的表达水平升高（P<0.05）；与模型组相比，各治疗组PI3K、p-Akt和SIRT6蛋白的表达水平显著升高，p-NF-κB p65、TNF-α和IL-6的蛋白的表达水平显著降低（P<0.05）。结论 竹节参总皂苷可以通过调节PI3K/Akt和NF-κB通路，有效减缓CCl4诱导的大鼠急性肝损伤，发挥其抗炎、抗氧化应激和保护肝损伤的作用。

关键词: 急性肝损伤；竹节参总皂苷；PI3K/Akt/NF-κB；抗炎；抗氧化

Abstract: Objective To investigate the protective effect of total saponins of Panax japonicus (TSPJ) against CCl4-induced acute liver injury (ALI) in rats and explore the underlying pharmacological mechanisms. Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water, 100 mg/kg biphenyl bisabololol, or 50, 100, and 200 mg/kg TSPJ during modeling (n=8). Liver functions (AST, ALT, TBil and ALP) of the rats were assessed and liver pathologies were observed with HE staining. Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue; ELISA was used to determine the levels of T-SOD, GSH-Px, and MDA. Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue. Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI. In the rat models of ALI, treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST, ALT, ALP, TBil and MDA and decrease of T-SOD and GSH-Px levels (all P<0.01). The rat models of ALI showed significantly increased expression of p-NF-κB (P<0.01), decreased expressions of PI3K, p-Akt and SIRT6 proteins, and elevated expression levels of p-NF-κB, TNF-α and IL-6 proteins in the liver, which were all significantly improved in the treatment groups (P<0.05 or 0.01). Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver via regulating the PI3K/Akt and SIRT6/NF-κB pathways.

Key words: acute liver injury; total saponins of Panax japonicus; PI3K/Akt/NF-κB; anti-inflammation; anti-oxidation