黄芪水煎剂对荷H22肝癌小鼠瘤组织凋亡及肝损伤调控的作用机制  

Mechanism of astragalus decoction on apoptosis and liver injury in H tumor-bearing mice

作　　者：安方玉[1,2] 史旭锋 颜春鲁[1] 刘永琦[1,2] 汪永锋[1] 赵崇博 AN Fangyu;SHI Xufeng;YAN Chunlu;LIU Yongqi;WANG Yongfeng;ZHAO Chongbo(Gansu University of Traditional Chinese Medicine,Lanzhou,Gansu,730000 P.R.China;Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Study on Prevention and Treatment of Traditional Chinese Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou,Gansu,730000 P.R.China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,甘肃兰州730000

出　　处：《华西药学杂志》2020年第4期392-396,共5页West China Journal of Pharmaceutical Sciences

基　　金：甘肃省科技支撑计划项目(1204FKCA169);甘肃省高校大学生就业创业能力提升工程项目(6-1);甘肃中医药大学教学研究与教学改革项目(ZH-201606)。

摘　　要：目的探讨黄芪水煎剂对荷H22肝癌小鼠瘤组织凋亡相关蛋白表达及肝功能的影响,并揭示其可能的抗肿瘤机制。方法将50只昆明种小鼠,随机均分为空白组、模型组、黄芪水煎剂组、顺铂组和黄芪水煎剂联合顺铂组。除空白组外,其余各组接种H22肝癌细胞至腋下复制荷瘤模型小鼠,建模24 h后给予相应药物治疗10 d。检测给药前、后的体质量,计算有效体质量及胸脾指数;用比色分析法检测肝组织谷草转氨酶(AST)、谷丙转氨酶(ALT)的活力;ELISA法检测血清肿瘤坏死因子-α(TNF-α)和白介素-2(IL-2)的含量;HE染色观察肿瘤组织病理形态学变化;免疫组化法检测肿瘤组织中核转录因子κB(NF-κB)和半胱氨酸蛋白酶(Caspase-3)的表达。结果与空白组比较,模型组的胸脾指数、IL-2和TNF-α的含量均明显下降,且ALT和AST的活力均明显升高;模型组可见肿瘤细胞大小形态不一、核大深染、细胞核呈现异型性。与模型组比较,黄芪水煎剂组与黄芪水煎剂联合顺铂组的胸脾指数、IL-2和TNF-α含量均明显升高,给药后体质量、有效体质量、ALT和AST的活力均明显降低,各治疗组肿瘤细胞出现凝固性坏死,各治疗组肿瘤组织中NF-κB的表达明显降低、Caspase-3的表达明显升高。与顺铂组比较,黄芪水煎剂联合顺铂组的有效体质量、脾指数、IL-2和TNF-α含量均明显升高,而ALT和AST的活力明显降低。结论黄芪水煎剂能诱导肿瘤组织凋亡并减轻荷H22肝癌小鼠的肝损伤,其可能的机制是通过调控瘤组织中NF-κB、Caspase-3的表达来诱导肿瘤组织凋亡并减轻肝损伤。OBJECTIVE To investigate the effects of astragalus decoction on the expression of apoptosis-related proteins and liver function in H22 tumor-bearing mice,and to reveal its possible anti-tumor mechanism.METHODS 50 KM mice were randomly divided into blank group,model group,astragalus decoction group,Cisplatin group and astragalus decoction combined with Cisplatin group,with 10 mice in each group.Except for the blank group,the other groups were inoculated with H22 liver cancer cells to replicate tumor-bearing mice under armpits.After 24 hours of modeling,corresponding drugs were given for 10 days.The body weight and the effective body mass were detected,and the indexes of thymus and spleen were checked.The activities of glutamic-oxaloacetic transaminase(AST)and glutamic-pyruvic transaminase(ALT)in liver tissue were detected by colorimetric analysis.ELISA was used to detect the contents of tumor necrosis factor-α(TNF-α)and interleukin-2(IL-2)in serum.HE staining was used to observe the histopathological changes of tumor tissues.The expression of nuclear factor-κB(NF-κB)and cysteine protease 3(Caspase-3)in tumor tissues was detected by immunohistochemistry.RESULTS Compared with the blank group,the indexes of thymus and spleen were declined obviously,the contents of IL-2 and TNF-αwere significantly decreased,and the activities of ALT and AST were significantly increased in the model group.In the model group,the tumor cell size and morphology were different,the stone was deeply stained,and the nucleus was abnormal.Compared with model group,the indexes of thymus and spleen and the levels of IL-2 and TNF-αwere significantly increased in the astragalus decoction group and astragalus decoction combined with Cisplatin group,the body weight and the effective body mass were obviously declined and the activities of ALT and AST were significantly decreased in the astragalus decoction group and astragalus decoction combined with Cisplatin group.Coagulation necrosis was appeared,the expression of NF-κB was significantly dec

关 键 词：黄芪水煎剂 H22荷瘤小鼠 凋亡 AST ALT IL-2 TNF-α NF-κB 

分 类 号：R96[医药卫生—药理学]