文献类型：期刊文献

中文题名：基于HMGB1/TLR4/NF-κB通路探讨参芪抑瘤方联合顺铂对H22肝癌荷瘤小鼠的抑瘤作用及免疫功能的影响

英文题名：Investigation of the Tumor Suppression Effect and Immune Function of Shenqi Yiliu Decoction Combined with Cisplatin on H22 Liver Cancer Tumor-Bearing Mice Based on HMGB1/TLR4/NF-κB Pathway

作者：杨玉萍[1,2];段永强[3];梁建庆[1,2];白敏[1,2];冯鑫[1,2];曹力仁[1,2];虎峻瑞[3];范红丽[3]

第一作者：杨玉萍

机构：[1]甘肃中医药大学基础医学院,兰州730000;[2]甘肃省实验动物行业技术中心,兰州730000;[3]宁夏医科大学中医学院,银川750004

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2023

卷号：25

期号：7

起止页码：2365

中文期刊名：世界科学技术-中医药现代化

外文期刊名：Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD_E2023_2024】；

基金：兰州市科技局2015年人才创新创业项目扶持基金项目(2015-RC-24):新药“复方参芪抑瘤胶囊”的研制,负责人:吴红彦;甘肃省发改委2013年第十一批建设项目计划(2305142201):自主创新能力建设项目,负责人:吴红彦。

语种：中文

中文关键词：参芪抑瘤方;顺铂;肝癌;免疫功能;HMGB1/TLR4/NF-κB信号通路

外文关键词：Shenqi Yiliu decoction;Cisplatin;Hepatocellular carcinoma;Immune function;HMGB1/TLR4/NF-κB signaling pathway

摘要：目的基于HMGB1/TLR4/NF-κB通路探讨参芪抑瘤方联合顺铂对H22肝癌荷瘤小鼠的抑瘤作用及相关免疫指标的影响。方法50只SPF级雄性KM小鼠,采用随机数字表法取10只小鼠作为空白组,其40只小鼠复制H22肝癌荷瘤小鼠模型,模型复制成功后将模型小鼠随机分为模型组、顺铂组(2.5×10^(-3)g·kg^(-1))、参芪抑瘤方中药组(27.03 g·kg^(-1))、参芪抑瘤方(27.03 g·kg^(-1))联合顺铂组(2.5×10^(-3)g·kg^(-1)),每组10只,治疗13天,测定抑瘤率、脾指数和胸腺指数;苏木精-伊红染色(Hematoxylin-eosin staining,HE)观察肿瘤病理学变化;流式细胞术检测脾组织中CD4^(+)T、CD8^(+)T细胞水平;实时荧光定量PCR(Realtime PCR,RT-PCR)和蛋白免疫印迹法(Western blot)检测肿瘤组织中高迁移率族蛋白B1(High mobility group protein,HMGB1)/TOLL样受体4(Toll-like receptor 4,TLR4)/核因子κB(Nuclear factor kappa-B,NF-κB)通路相关的基因与蛋白表达。结果①与空白组相比,模型组小鼠平均体质量及小鼠脾指数、胸腺指数、CD4^(+)T细胞水平以及CD4^(+)T/CD8^(+)T值均显著降低、CD8^(+)T细胞水平升高(P<0.05);②与模型组相比,各治疗组小鼠平均瘤质量降低(P<0.05),瘤体积减小(P<0.05),体质量升高(P<0.05),中药组和联合组小鼠脾指数、胸腺指数、CD4^(+)T细胞水平以及CD4^(+)T/CD8^(+)T比值均升高,CD8^(+)T细胞水平降低,且中药组治疗效果显著(P<0.05),小鼠肿瘤组织中HMGB1、TLR4、MyD88、NF-κB mRNA与蛋白表达均降低,且联合组效果显著(P<0.05);③与顺铂组相比,联合组小鼠肿瘤组织中HMGB1、TLR4、MyD88、NF-κB mRNA与蛋白表达均降低(P<0.05);④与中药组相比,联合组小鼠肿瘤组织中HMGB1、TLR4、MyD88、NF-κB mRNA与蛋白表达均降低(P<0.05)。结论参芪抑瘤方联合顺铂能有效抑制H22肝癌荷瘤小鼠肿瘤生长,提高相关免疫指标,其机制可能与抑制HMGB1/TLR4/NF-κB信号通路活化有关。
Objective Based on HMGB1/TLR4/NF-κB pathway,to investigate the effects of Shenqi Yiliu decoction combined with cisplatin on H22 liver cancer tumor mice and the effects of related immune indicators.Methods 50 SPF grade male KM mice,10 mice were taken as blank group by random number table method,and the other 40 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mice model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group(2.5×10^(-3)g·kg^(-1)),Shenqi Yiliu decoction TCM group(27.03 g·kg^(-1)),and Shenqi Yiliu decoction TCM(27.03 g·kg^(-1))combined with cisplatin(2.5×10^(-3)g·kg^(-1)),10 mice in each group were treated for 13 d.Determine tumor suppression rate,spleen index and thymus index;HE observes changes in oncology pathology;streaming cells detect the level of CD4^(+)T,CD8^(+)T cells in the spleen tissue;PT-PCR and WB method detect genes and protein expression related to HMGB1/TLR4/NF-κB signaling pathways in tumor tissues.Results①Compared with the blank group,the mean body mass and mouse spleen index,thymus index,CD4^(+)T cell level and CD4^(+)T/CD8^(+)T value were significantly lower and CD8^(+)T cell level was higher in the model group(P<0.05);②Compared with the model group,the mean tumor mass decreased(P<0.05),tumor volume decreased(P<0.05),and body mass increased(P<0.05)in each treatment group,and the spleen index,thymus index,CD4^(+)T cell level and CD4^(+)T/CD8^(+)T ratio increased and CD8^(+)T cell level decreased in both the Chinese medicine group and the combination group,and the treatment effect was significant in the Chinese medicine group(P<0.05),and HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression in tumor tissues of mice were reduced,and the effect was significant in the combined group(P<0.05).③Compared with the cisplatin group,HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression were reduced in the tumor tissues of mice in the combination group(P<0.05).④HMGB1,TLR4,MyD88,NF-κB mRNA and protein expression in tumor tissues of mice in the combined group were reduced compared with those in the Chinese medicine group(P<0.05).Conclusion Shenqi Yiliu decoction combined with cisplatin can effectively inhibit tumor growth and improve related immune indexes in H22 hepatocellular carcinoma tumor-bearing mice,and the mechanism may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway activation.