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李锦源,黄文涛,韦园园,吴琼.氧化苦参碱联合全反式维甲酸干预大鼠肝癌变进程中细胞因子的变化[J].中国比较医学杂志,2019,29(8):111~116.
氧化苦参碱联合全反式维甲酸干预大鼠肝癌变进程中细胞因子的变化
Effects of oxymatrine combined with all-trans retinoic acid on cytokines during hepatocarcinogenesis in rats
投稿时间:2019-01-25  
DOI:10.3969/j. issn. 1671 -7856. 2019. 08. 018
中文关键词:  氧化苦参碱  全反式维甲酸  二乙基亚硝胺  肝癌  大鼠
英文关键词:oxymatrine  all-trans retinoic acid  diethylnitrosamine  liver cancer  rats
基金项目:
作者单位E-mail
李锦源 广西医科大学附属肿瘤医院, 南宁 530022 14789834339@ 163.com 
黄文涛 广西医科大学附属肿瘤医院, 南宁 530022  
韦园园 广西医科大学附属肿瘤医院, 南宁 530022  
吴琼 广西医科大学附属肿瘤医院, 南宁 530022 wuqiong1919@ 163.com 
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中文摘要:
      目的 观察氧化苦参碱(oxymatrine, OMT)联合全反式维甲酸(all-trans retinoic acid, ATRA)抑制二乙基亚硝胺(DEN)诱导的大鼠肝癌形成效果,并探讨其作用机制?方法 采用DEN 诱导建立肝癌大鼠模型,造模18 周,将Wistar 大鼠随机分为空白组?模型组?干预组,分别在诱癌后6?12?18 周处死大鼠,通过HE 染色观察大鼠肝组织病理变化,检测大鼠肝功能相关指标,ELISA 检测大鼠IL-6 含量;采用RT-qPCR 法检测大鼠let-7a?NF-κBp65?IL-6,STAT3 mRNA 表达变化;采用Western blot 检测大鼠STAT3?p-STAT3 的蛋白变化?结果 HE 染色病理学观察显示,干预组大鼠肝癌结节数明显少于模型组,肝细胞病变坏死减轻;与模型组比较,干预组大鼠血清IL-6 及肝功能指标ALT?GGT?AST?ALP 水平均明显降低( P <0. 05);RT-qPCR 检测结果:与模型组比较,干预组大鼠肝组织中let-7a mRNA 表达水平明显上升,而NF-κB-p65?IL-6 和STAT3 mRNA 表达量均明显降低( P <0. 05)?实验第18 周,Western blot 检测结果干预组STAT3?p-STAT3 蛋白表达均明显低于模型组( P <0. 05)?结论 氧化苦参碱联合全反式维甲酸能够明显抑制DEN 诱发的大鼠肝癌形成,在一定程度上延缓肿瘤生长?
英文摘要:
      Objective To observe the inhibitory effect of oxymatrine (OMT) combined with all-trans retinoic acid(ATRA) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma in rats, and to explore its mechanism of action.Methods A rat model of hepatocellular carcinoma was established by DEN induction for 18 weeks. Wistar rats wererandomly divided into control, model, and intervention groups. Rats were killed at 6, 12, and 18 weeks after cancerinduction. Pathological changes of the liver tissues were observed by hematoxylin and eosin (HE) staining, related indexesof rat liver function were detected, and interleukin (IL)-6 expression was detected by enzyme-linked immunosorbent assay.The mRNA expressions of let-7a, nuclear factor (NF)-κB-p65, IL-6, and signal transducer and activator of transcription(STAT)3 were detected by quantitative real-time (RT-q)PCR, while the changes of STAT3 and p-STAT3 proteins weredetected by western blotting. Results The pathological examination revealed a significantly decreased number of livercancer nodules in the intervention group compared with the model group ( P <0. 05), while levels of serum IL-6, alanineaminotransferase(ALT), glutamyl transpeptidase(GGT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) were significantly lower ( P < 0. 05). RT-qPCR results showed that the expression of let-7a was significantlyincreased in the intervention group compared with the model group, while that of NF-κB-p65, IL-6, and STAT3 wassignificantly decreased ( P <0. 05). At the 18th week of the experiment, the expressions of STAT3 and p-STAT3 in theintervention group were significantly lower than in the model group ( P <0. 05). Conclusions OMT combined with ATRA can significantly inhibit DEN-induced hepatocarcinogenesis in rats and delay the growth of tumors to some extent.
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