清肝化瘀颗粒对原发性肝癌模型大鼠Raf/MEK/ERK通路的影响  

Effect of Qinggan Huayu Granules on Raf/MEK/ERK pathway in rat model of primary hepatic carcinoma

作　　者：边倩 吴昭利 程丹丹 魏海梁 闫曙光[5] 李京涛 BIAN Qian;WU Zhao-li;CHENG Dan-dan;WEI Hai-liang;YAN Shu-guang;LI Jing-tao(No.2 Department of Liver Diseases,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;NO.1 Department of Oncology,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;School of Clinical Chinese Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Department of General Surgery,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;School of Basic Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China;No.1 Department of Liver Diseases,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学附属医院肝病二科,咸阳市712000 [2]陕西中医药大学附属医院,肿瘤一科,咸阳市712000 [3]陕西中医药大学中医临床医学院,咸阳市712046 [4]陕西中医药大学附属医院普外科,咸阳市712000 [5]陕西中医药大学基础医学院,咸阳市712046 [6]陕西中医药大学附属医院肝病一科,咸阳市712000

出　　处：《广西医学》2020年第8期981-984,共4页Guangxi Medical Journal

基　　金：陕西省中医管理局中医药科研课题项目(15-LC014)。

摘　　要：目的探讨清肝化瘀颗粒治疗原发性肝癌大鼠对迅速加速纤维肉瘤蛋白(Raf)/丝裂原活化的细胞外信号调节激酶(MEK)/细胞外信号调节激酶(ERK)信号通路表达的影响。方法将50只雄性Wistar大鼠随机分为空白对照组、模型对照组、清肝化瘀颗粒低剂量组、清肝化瘀颗粒剂中剂量组和清肝化瘀颗粒剂高剂量组,每组10只。除空白对照组外,其他4组饮用含二乙基亚硝胺的灭菌食用水建立原发性肝癌大鼠模型,空白对照组只饮用灭菌食用水。14周后,清肝化瘀颗粒低剂量组、中剂量组、高剂量组分别给予0.5 g/kg、1.0 g/kg、2.0 g/kg的清肝化瘀颗粒灌胃,空白对照组及模型对照组给予等体积的生理盐水灌胃。连续灌胃2周后,处死大鼠并取出肝脏组织,用苏木精-伊红染色法观察肝脏组织形态学,并检测各组大鼠肝脏组织Raf、MEK和ERK mRNA和蛋白表达水平。结果苏木精-伊红染色结果显示空白对照组大鼠肝细胞结构正常,模型对照组可见肿瘤细胞,肝细胞结构被破坏。与空白对照组比较,其余4组大鼠肝脏组织Raf、MEK和ERK的A值及mRNA、蛋白表达水平升高,清肝化瘀颗粒中剂量组和清肝化瘀颗粒高剂量组低于模型对照组,且清肝化瘀颗粒中剂量组低于清肝化瘀颗粒高剂量组(均P<0.05)。结论清肝化瘀颗粒可能通过抑制Raf/MEK/ERK信号通路的活化而发挥抗肿瘤作用。Objective To investigate the effect of Qinggan Huayu Granules on the expression of rapidly accelerated fibrosarcoma(Raf)/mitogen-activated extracellular signal-regulated kinase(MEK)/extracellular signal-regulated kinase(ERK) signaling pathway in rats with primary hepatic carcinoma.Methods Fifty male Wistar rats were randomly divided into blank control group, model control group, low-dose Qinggan Huayu Granules group, medium-dose Qinggan Huayu Granules group and high-dose Qinggan Huayu Granules group, with 10 rats in each group. Except the blank control group, the rats in the other four groups were fed with sterilized drinking water containing diethylnitrosamine to establish the rat model of primary hepatic carcinoma, and the blank control group was fed with sterilized drinking water only. Fourteen weeks later, the low-dose, medium-dose and high-dose Qinggan Huayu Granules groups were given intragastric administration of Qinggan Huayu Granules at concentrations of 0.5 g/kg,1.0 g/kg and 2.0 g/kg, respectively, the blank control group and the model control group were given intragastric administration of equivalent volume of normal saline. After intragastric administration for two weeks consecutively, the rats were killed to remove liver tissues, the morphology of the liver tissues was observed using hematoxylin-eosin staining, and the expression levels of liver tissue Raf, MEK and ERK mRNAs and proteins were detected in each group. Results The results of hematoxylin-eosin staining showed that the rats in the blank control group exhibited normal structure of hepatocytes, the model control group presented visual tumor cells and damaged structure of hepatocytes. Compared with the blank control group, the remaining four groups had increased A values of liver tissue Raf, MEK and ERK, as well as elevated expression levels of RAF, MEK and ERK mRNAs and proteins, the medium-dose and high-dose Qinggan Huayu Granules groups exhibited lower levels than the model control group, and the medium-dose Qinggan Huayu Granules group e

关 键 词：原发性肝癌 清肝化瘀颗粒 迅速加速纤维肉瘤蛋白 丝裂原活化的细胞外信号调节激酶 细胞外信号调节激酶 信号通路 大鼠 

分 类 号：R735.7[医药卫生—肿瘤]