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目的 研究破壁灵芝孢子粉(GLS)对小鼠肝癌模型的治疗作用并探索其机制。方法 将50只2周龄C57BL/6J小鼠分为对照组、模型组及GLS低、中、高剂量(0.25、0.5、1.0 g/kg)组，每组10只，建立二乙基亚硝胺(DEN)/CCl4小鼠肝癌模型，第8周开始灌胃GLS，每天1次，连续14周。末次给药结束后观察小鼠肝脏结节数量，酶联免疫吸附测定法检测小鼠血清甲胎蛋白(AFP)；钼酸铵法检测小鼠血清、肝组织过氧化氢酶(CAT)含量；微板法检测小鼠血清、肝组织还原型谷胱甘肽(GSH)含量；比色法检测小鼠血清、肝组织谷胱甘肽过氧化物酶(GSH-PX)含量；免疫组化法检测增殖细胞核抗原(PCNA)蛋白表达；实时荧光定量聚合酶链式反应检测核因子E2相关因子2(Nrf2)、血红素加氧-1(Ho-1)、Kelch样环氧氯丙烷相关蛋白1(Keap1)、醌氧化还原酶1(Nqo1)和谷氨酸半胱氨酸连接酶催化亚基(Gclc)mRNA相对表达。结果 与对照组比较，模型组小鼠血清AFP含量升高(P<0.01)，小鼠肝脏及血清CAT、GSH、GSH-PX含量下降(P<0.01),Keap1、Nqo1 mRNA相对表达升高(P<0.01),Nrf2、Ho-1、Gclc mRNA相对表达降低(P<0.01),PCNA阳性表达率升高(P<0.01)；与模型组比较，给药组小鼠肝脏结节总数、血清AFP含量降低(P<0.01)，小鼠肝脏及血清CAT、GSH、GSH-PX含量升高(P<0.05或P<0.01),Keap1、Nqo1 mRNA表达降低(P<0.05),Nrf2、Ho-1、Gclc mRNA表达升高(P<0.05),PCNA阳性表达率降低(P<0.01)。结论 GLS对DEN/CCl4诱导的小鼠肝癌模型具有显著保护作用，作用机制与调节小鼠肝脏氧化应激有关。
Abstract：Objective To investigate the therapeutic effect of wall-broken ganoderma lucidum spore powder(GLS) on a mouse model of hepatocellular carcinoma and to explore its underlying mechanism.Methods Fifty 2-week-old C57BL/6J mice were divided into a control group, a model group and low, medium and high-dose GLS groups(0. 25, 0. 5, 1. 0 g/kg), with 10 mice in each group. A DEN/CCL4 mouse hepatocellular carcinoma model was established, and GLS was administered by gavage starting from the 8th week, once a day for 14 weeks. At the end of the final administration, the number of liver nodules was observed, and the serum alpha-fetoprotein(AFP) was detected using enzyme-linked immunosorbent assay. The content of catalase(CAT) in serum and liver tissue was determined by ammonium molybdate method. The content of reduced glutathione(GSH) in serum and liver tissue was measured by microplate assay. The content of glutathione peroxidase(GSH-PX) in serum and liver tissue was detected by colorimetric method. Immunohistochemistry(IHC-P) was employed to detect the protein expression of proliferating cell nuclear antigen(PCNA). R eal-time fluorescence quantitative polymerase chain reaction was utilized to detect the relative expression of nuclear factor E2-related factor 2(Nrf2), Kelch-like epichlorohydrin-associated protein 1(Keap1), NAD(P)H quinone oxidoreductase 1(Nqo1), heme oxygenase-1(Ho-1) and glutamate cysteine ligase catalytic subunit(Gclc) mRNA.Results Compared with the control group, the content of serum AFP were significantly higher in the model group(P<0. 01), while the contents of CAT, GSH and GSH-PX in liver and serum were significantly lower in the model group(P<0. 01). The relative expression of Keap1 and Nqo1 mRNA was significantly higher(P<0. 01), the relative expression of Nrf2, Ho-1, Gclc mRNA relative expression was significantly lower(P<0. 01), and the positive expression rate of PCNA was significantly higher(P<0. 01). Compared with the model group, the total number of liver nodules and content of serum AFP in the administered group were significantly lower(P<0. 01), and the contents of CAT, GSH, and GSH-PX in the liver and serum of mice significantly increased(P<0. 05 or P<0. 01). The expression of Keap1 and Nqo1 mRNA significantly decreased(P<0. 05). The expression of Nrf2, Ho-1 and Gclc mRNA significantly increased(P<0. 05), and positive expression rate of PCNA significantly decreased(P<0. 01).Conclusion GLS has a significant protective effect on DEN/CCL4-induced mouse hepatocellular carcinoma model, and the mechanism of action is related to the regulation of oxidative stress in mouse liver.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.07.003
中图分类号:R285.5
引用信息:
[1]金海,万硕,刘倩,等.破壁灵芝孢子粉通过调控Nrf2通路保护DEN/CCl_4诱导的小鼠肝癌模型[J].安徽医科大学学报,2026,61(07):1176-1182.DOI:10.19405/j.cnki.issn1000-1492.2026.07.003.
基金信息:
国家自然科学基金项目(编号：82460466); 贵州省科技计划项目(编号：黔科合基础-ZK[2024]一般323)~~
2026-05-26
2026-05-26
2026-05-26