摘要
目的探讨白花蛇舌草乙醇提取物对大鼠肝癌细胞增殖的影响及作用机制。方法选取Wistar大鼠82只,采用小剂量二乙基亚硝铵(DEN)构建大鼠肝癌模型,在动物造模成功后随机分为模型组、低剂量组、中剂量组、高剂量组,各20只。造模成功后1 d,模型组给予乙醇提取物溶剂1 mL/(100 g·d)灌胃处理8周,后三组分别给予90、180、360 mg/(kg·d)白花蛇舌草乙醇提取物灌胃处理8周。观察各组大鼠一般情况;常规检测各组大鼠血清ALT、AST水平;采用HE染色观察各组大鼠肝脏组织形态学变化;采用免疫组化染色法测算各组大鼠肝组织PCNA阳性细胞表达率;采用Western blotting法检测各组大鼠肝组织PI3K、Akt和DDR1蛋白。结果模型组大鼠精神表现萎靡、毛发散乱,饮食量降低,低、中、高剂量组大鼠上述状态得到一定的改善。与模型组相比,低、中、高剂量组大鼠ALT和AST水平降低(P<0.05或<0.01)。HE染色显示模型组大鼠肝组织多处坏死,伴有明显的形态异常;低、中、高剂量组大鼠肝组织坏死减轻,细胞变性程度减轻。与模型组相比,低、中、高剂量组PCNA阳性细胞率降低,PI3K、Akt、DDR1蛋白表达降低(P<0.05或<0.01)。结论白花蛇舌草乙醇提取物能够抑制大鼠肝癌细胞增殖,其机制可能与下调DDR1表达,抑制PI3K/Akt信号通路有关。
Objective To explore the effects of ethanol extracts of hedyotis diffusa on the proliferation of rat liver cancer cells and its mechanism.Methods Eighty-two Wistar rats were selected,and we used low-dose diethyl nitrosamine(DEN)to construct rat liver cancer models.After successful animal modeling,they were randomly divided into the model group,low-dose group,medium-dose group,and high-dose group,with 20 in each.One day after successful modeling,the rats in the model group were given ethanol extract solvent 1 mL/(100 g·d)orally for 8 weeks,and the rats in the last three groups were given 90,180,and 360 mg/(kg·d)ethanol extracts of hedyotis diffusa intragastrically for 8 weeks.We observed the general conditions of rats in each group,routinely detected the levels of serum ALT and AST in each group,used HE staining to observe the morphological changes of the liver tissues of each group,used immunohistochemical staining to measure the expression rates of PCNA positive cells in the liver tissues,and used Western blotting to detect PI3K,Akt and DDR1 proteins in the liver tissues of rats in each group.Results The mental performance of rats in the model group was sluggish,the hair was scattered,and the diet was reduced.The above-mentioned state of the rats in the low-dose,medium-dose and high-dose groups was improved to a certain extent.Compared with the model group,the content of ALT and AST decreased in the low-dose,medium-dose and high-dose groups(P<0.05 or P<0.01).HE staining showed multiple necrosis of liver tissues in the model group,accompanied by obvious morphological abnormalities;the liver tissue necrosis and cell degeneration were alleviated in the low-dose,medium-dose and high-dose groups.Compared with the modelgroup,the rates of PCNA positive cells decreased in the low-dose,medium-dose and high-dose groups,and the expression of PI3K,Akt,and DDR1 proteins decreased(P<0.05 or P<0.01).Conclusion The ethanol extracts of hedyotis diffusa can inhibit the proliferation of rat liver cancer cells,and the mechanism may be related to down-regulation of DDR1 expression and inhibition of PI3K/Akt signaling pathway.
作者
吴元芳
张陈丽
张芹
WU Yuanfang;ZHANG Chenli;ZHANG Qin(Pharmacy Department,The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230031,China)
出处
《山东医药》
CAS
2022年第4期51-54,共4页
Shandong Medical Journal
基金
安徽高校自然科学研究项目(KJ2018BP89)。
关键词
肝肿瘤
原发性肝癌
白花蛇舌草乙醇提取物
细胞增殖
盘状结构域受体1
liver neoplasms
primary liver carcinoma
ethanol extracts of hedyotis diffusa
cell proliferation
discoid domain receptor 1
