保元解毒汤对癌性恶病质小鼠肝脏脂质及肝脏线粒体功能的影响  

Effect of Baoyuan Jiedu Decoction on Liver Lipids and Liver Mitochondrial Function in Cancer Cachexia Mice

作　　者：罗丽 黄盛琦 王杨 李翱翔 季旭明 LUO Li;HUANG Shengqi;WANG Yang(School of Basic Medical Sciences,Zhejiang Chinese Medical University,Hangzhou,310053,China;Haian City Maternal and Child Health Care and Family Planning Service Center)

机构地区：[1]浙江中医药大学基础医学院,杭州310053 [2]海安市妇幼保健及计划生育服务中心 [3]浙江中医药大学中医药科学院

出　　处：《浙江中医药大学学报》2025年第2期123-131,共9页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金项目(81573871、82274406);浙江省自然科学基金项目(LZ24H270001);教育部产学合作协同育人项目(231001282180502、230907540282046)。

摘　　要：[目的]探究保元解毒汤对癌性恶病质小鼠肝脏脂质及肝脏线粒体功能的影响。[方法]使用Lewis肺癌细胞皮下接种建立癌性恶病质小鼠模型,将小鼠随机分为正常组、模型组、保元解毒汤组和甲羟孕酮组,连续给药21 d,记录小鼠摄食量、体质量及肿瘤体积;多维质谱“鸟枪”法脂质组学(multi-dimensional mass spectrometry-based shotgun lipidomics,MDMS-SL)技术检测肝脏脂质含量;透射电镜观察肝脏线粒体改变;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测肝脏三磷酸腺苷(adenosine triphosphate,ATP)含量;实时荧光定量聚合酶链式反应(Real-time quantitative polymerase chain reaction,RT-qPCR)检测肝脏线粒体呼吸链复合物泛醌氧化还原酶亚基B8(NADH:ubiquinone oxidoreductase subunit B8,NDUFB8)、琥珀酸脱氢酶复合物铁硫亚基B(succinate dehydrogenase complex iron sulfur subunit B,SDHB)、泛醇-细胞色素C还原酶核心蛋白2(ubiquinolcytochrome-c reductase complex core protein 2,UQCRC2)的mRNA表达水平;免疫印迹法检测肝脏线粒体呼吸链复合物NDUFB8蛋白表达水平。[结果]与模型组比较,保元解毒汤组小鼠摄食量、体质量增加,肿瘤增长缓慢(P<0.05)。脂质组学结果显示,模型组肝脏脂质较正常组发生显著改变,保元解毒汤干预后可明显调节其中33种脂质分子(P<0.05)。透射电镜结果显示,模型组线粒体形态扭曲,部分线粒体内容物降解、线粒体外膜破裂,线粒体嵴明显缩短、断裂,保元解毒汤组线粒体形态较模型组明显缓解,嵴状结构破坏减轻。ELISA结果显示,保元解毒汤组肝脏ATP含量较模型组明显增加(P<0.05)。RT-qPCR结果显示,保元解毒汤干预后可明显升高线粒体呼吸链复合物NDUFB8、SDHB、UQCRC2的mRNA表达水平(P<0.05)。免疫印迹显示,保元解毒汤干预可显著升高线粒体呼吸链复合物NDUFB8的蛋白表达水平(P<0.05)。[结论]保元解毒汤能明显增加癌性恶病质小[Objective]To explore the effect of Baoyuan Jiedu Decoction(BJD)on liver lipids and liver mitochondrial function in cancer cachexia mice.[Methods]The mice model of cancer cachexia was established by subcutaneous inoculation of Lewis lung cancer cells,and the mice were randomly divided into normal group,model group,BJD group and medroxyprogesterone acetate(MPA)group,which were given continuously for 21 days,and the food intake,body weight and tumor volume of the mice were recorded.Multi-dimensional mass spectrometry-based shotgun lipidomics(MDMS-SL)was used to detect liver lipid content.Changes of liver mitochondria were observed by transmission electron microscope.Enzyme-linked immunosorbent assay(ELISA)was used to detect adenosine triphosphate(ATP)content in liver.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of liver mitochondrial respiratory chain complexes NADH:ubiquinone oxidoreductase subunit B8(NDUFB8),succinate dehydrogenase complex iron sulfur subunit B(SDHB)and ubiquinol-cytochrome-c reductase complex core protein 2(UQCRC2).The expression level of liver mitochondrial respiratory chain complex NDUFB8 protein was detected by Western blot.[Results]Compared with model group,the food intake and body weight of BJD group increased,and the tumor growth was slow(P<0.05).The results of lipidomics showed that the liver lipids in model group changed significantly compared with those in normal group,and BJD could obviously regulate 33 lipid molecules after intervention(P<0.05).The transmission electron microscope showed that the morphology of mitochondria in the model group was distorted,some mitochondrial contents were degraded,the outer membrane of mitochondria was broken,and the crista of mitochondria was obviously shortened and broken.Compared with the model group,the morphology of mitochondria in Baoyuan Jiedu Decoction group was obviously relieved,and the damage of crista structure was alleviated.The results of ELISA showed that the ATP content in the li

关 键 词：癌性恶病质 保元解毒汤 肝脏 多维质谱“鸟枪”法脂质组学 脂质代谢 线粒体 线粒体呼吸链复合物 甲羟孕酮 

分 类 号：R331[医药卫生—人体生理学]