和枢消积丸对H22荷瘤小鼠的抑瘤作用及肿瘤组织VEGF、PDGF蛋白的影响  

The effect of Heshu Xiaoji prescription on tumor suppression and tumor tissue VEGF and PDGF proteins in H22 tumor-bearing mice

作　　者：陈相霖 汪静 朱晓宁 张玉蓉 彭昭宣 CHEN Xiang-lin;WANG Jing;ZHU Xiao-ning(College of Integrative Chinese and Western Medicine,Southwest Medical University(Luzhou Sichuan,646000),China;不详)

机构地区：[1]西南医科大学中西医结合学院,四川泸州646000 [2]西南医科大学附属中医医院肝胆病科

出　　处：《中西医结合肝病杂志》2024年第4期336-340,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：国家中医临床基地研究建设单位科研项目(西南医大中医院[2020]33号);四川省科技厅重大专项项目(No.2019YF0018,2022YFS0619);四川省中医药管理局科技计划项目(No.2020IC0142);西南医科大学-西南医科大学附属中医医院联合项目(No.2019LZXNYDZ12)。

摘　　要：目的:探讨和枢消积丸对H22荷瘤小鼠的抑瘤作用和肿瘤血管生成相关因子表达的影响,探索中西医联合有效抗肝细胞癌治疗方案。方法:将H22荷瘤小鼠随机分成空白组、模型组、中药低剂量组(1.37 g/kg和枢消积丸)、中药中剂量组(2.73 g/kg和枢消积丸)、中药高剂量组(5.46 g/kg和枢消积丸)、索拉非尼组(0.03 g/kg)和联合组(5.46 g/kg和枢消积丸联合0.03 g/kg索拉非尼),干预14 d。观察各组小鼠生命活动,测量瘤体长短径和体重,灌胃结束后计算肿瘤体积和抑瘤率;检测小鼠肝功能指标AST、ALT;采用HE染色观察肿瘤组织结构和细胞形态;免疫组化及Western Blotting实验检测各组小鼠肿瘤组织中血管内皮生长因子(VEGF)和血小板衍生生长因子(PDGF)蛋白表达水平。结果:和枢消积丸对小鼠体重无明显影响,但可改善H22荷瘤小鼠的精神、活动状态,以及索拉非尼所致腹泻症状;与模型组比,各治疗组荷瘤小鼠皮下肿瘤的体积和质量均降低,联合组抑瘤率达74.8%,效果最明显(P<0.05);和枢消积丸可下调小鼠血清AST、ALT水平,改善肝脏功能(P<0.01);HE染色显示各治疗组小鼠肿瘤组织内部结构紊乱,与和枢消积丸的剂量呈正相关,联合组效果最明显;免疫组化和Western Blotting实验发现,各治疗组小鼠肿瘤组织VEGF、PDGF蛋白表达水平均下降(P<0.01),和枢消积丸联合索拉非尼对VEGF、PDGF的抑制作用比单独使用索拉非尼或和枢消积丸更显著。结论:和枢消积丸可下调肿瘤生成相关因子VEGF和PDGF蛋白表达,对H22荷瘤小鼠具有抑瘤作用,联合索拉非尼的中西医结合治疗最显著。Objective:To investigate the effects of Heshu Xiaoji prescription(HXP)on tumor suppression and expression of tumor angiogenesis-related factors in H22 tumor-bearing mice,to elucidate its potential mechanism,and to explore the effective anti-hepatocellular carcinoma therapeutic options combining Chinese and Western medicine.Methods:H22 tumor-bearing mice were randomly divided into blank group,model group,low,medium and high dose groups of HXP(1.37,2.73,5.46 g/kg),sorafenib group(0.03 g/kg),combined group(5.46 g/kg HXP combined with 0.03 g/kg sorafenib),and the intervention was carried out for 14 days.After the experiment,tumor volume and tumor suppression rate were calculated,aspartate aminotransferase(AST)and alanine aminotransferase(ALT)liver function indexes were measured,tumor cell structure and morphology were observed by Hematoxylin-eosin staining(HE)and vascular endothelial growth factor(VEGF)and platelet-derived growth factor(PDGF)protein expression levels were measured by immunohistochemistry and Western blotting in the tumor tissues of each group.Results:There was no significant effect on body weight change in mice,and HXP improved the mental and activity status and diarrhea symptoms caused by sorafenib in H22 tumor-bearing mice.Compared with the control group,all treatment groups inhibited the volume and mass of subcutaneous tumors in tumor-bearing mice,among which the relative tumor proliferation rate and tumor inhibition rate in the combined group were 31.3%and 74.8%,respectively,with the most obvious effect(P<0.05).HXP down-regulated AST and ALT expression levels and improved liver function in mice(P<0.01).HE staining showed that the internal structure of tumor tissues was disturbed in each treatment group,which was positively correlated with the dose of HXP,and the most significant in the combined group.IHC and Western Blotting experiments revealed that the protein expression of VEGF and PDGF were decreased in each treatment group compared with the model group(P<0.01);the combined group inhibited VE

关 键 词：和枢消积丸 肝细胞癌 索拉非尼 血管内皮生长因子 血小板衍生生长因子 

分 类 号：R259[医药卫生—中西医结合]