破壁灵芝孢子粉通过调控Nrf2通路保护DEN/CCl4诱导的小鼠肝癌模型OA

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 tis-sue 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 expres-sion 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 signifi-cant 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.