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熊胆粉及熊去氧胆酸对肝癌癌前病变的作用

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目的 为了探究熊胆粉(bear bile powder,BBP)及其熊去氧胆酸(chenodeoxycholic acid,UDCA)在肝癌癌前病变的发生发展中的影响,利用短期致癌动物模型探索了 BBP和UDCA的抗氧化作用及它在抗癌前病变中的影响。方法 SPF级SD大鼠40只随机分4组:对照(Control)组,模型(DEN)组,熊胆粉(DEN+BBP)组(200 mg/kg),熊去氧胆酸(DEN+UDCA)组(30 mg/kg),每组10只。实验开始除Control组外所有大鼠腹腔注射100 mg/kg二乙基亚硝胺(diethylnitrosamine,DEN),每周一次,共3周。从实验开始到结束,DEN+BBP组每天灌胃200 mg/kg BBP水溶剂,DEN+UDCA组每天灌胃30 mg/kg UDCA悬浮溶液。结果 DEN组,DEN+BBP组,DEN+UDCA组的体重和肝重量,3组之间无显著性差异。DEN组的肝组织中丙二醛(malondialdehyde,MDA)的水平显著增高,谷胱甘肽(glutathione,GSH)、超氧化物歧化酶(superoxide dismutase,SOD)的水平显著降低。但UDCA处理显著降低了 MDA的水平,显著增加了 GSH、SOD的水平。相反,BBP处理在血清中发挥同样的作用。DEN+BBP组和DEN+UDCA组的谷胱甘肽-S-转移酶(glutathione S-transferase,GST-P)阳性病变数量及面积和Ki-67阳性细胞率显著低于DEN组,且在DEN+UDCA组中更为明显。同时,DEN+UDCA组中的Caespase-9表达量显著高于DEN组。结论 BBP和UDCA对DEN诱导的肝癌癌前病变的发生均发挥显著的抑制作用,且对DEN诱导的氧化应激也有抗氧化作用,但它们的作用方式不同。同时,这些抗氧化作用是否参与抗癌作用需进一步研究。
Effect of bear bile powder and ursodeoxycholic acid on preneoplastic lesions of hepatocarcinoma
Objective To investigate the effect of bear bile powder(BBP)and ursodeoxycholic acid(UDCA)on preneoplastic lesions of hepatocarcinoma,using short-term carcinogenesis bioassay models.Methods Forty 6-week-old male SD rats were divided randomly into control,diethylnitrosamine(DEN),DEN+BBP(200 mg/kg),and DEN+UDCA(30 mg/kg)groups.All rats,except for the control group,were injected intraperitoneally with 100 mg/kg DEN once a week for 3 weeks.Rats in the DEN+BBP and DEN+UDCA groups also received oral BBP 200 mg/kg or UDCA 30 mg/kg suspended solution,respectively,daily from the beginning to the end of the experiment.Results There were no significant differences in body or liver weights between the DEN,DEN+BBP,and DEN+UDCA groups.DEN treatment increased the accumulation of malondialdehyde(MDA),decreased superoxide dismutase(SOD),and reduced glutathione(GSH)activities in liver tissue,while UDCA enhanced SOD and GSH activities and decreased MDA accumulation in liver tissue.In contrast,BBP exerted these antioxidant effects in serum.The number and area of glutathione S-transferase placental(GST-P)type-positive lesions and the Ki-67-positive cell ratio were significantly lower in the DEN+BBP and DEN+UDCA groups than in the DEN group,especially in the DEN+UDCA group.UDCA significantly increased Caspase-9 mRNA expression compared with the model group.Conclusions BBP and UDCA have significant inhibitory effects on preneoplastic lesions of hepatocarcinoma induced by DEN,and both have antioxidant effects on DEN-induced oxidative stress.The antioxidant mechanisms of BBP and UDCA differ,however,and further research is needed to determine the roles of the antioxidant effects in their anticancer mechanisms.

bear bile powderursodeoxycholic acidpreneoplastic lesions of hepatocarcinomaoxidative stress

贾贵阳、倪元萍、王梦茹、涉谷淳、金美兰

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西南大学动物医学院,重庆 400715

东京农工大学农学研究科动物生命科学部兽医病理学研究室,东京183-8509

西南大学实验动物中心,重庆 400715

熊胆粉 熊去氧胆酸 肝癌癌前病变 氧化应激

2024

中国实验动物学报
中国实验动物学会,中国医学科学院医学实验动物研究所

中国实验动物学报

CSTPCD北大核心
影响因子:0.767
ISSN:1005-4847
年,卷(期):2024.32(11)