田黄方通过调节肠道菌群改善小鼠非酒精性脂肪性肝病  

Tianhuang formula enhancing nonalcoholic fatty liver disease in mice through regulating gut microbiota

作　　者：罗智中 杨玲 韩怡 郭姣[1,2] 罗朵生 LUO Zhi-zhong;YANG Ling;HAN Yi;GUO Jiao;LUO Duo-sheng(Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine,Guangzhou 510006,China;Guangdong Traditional Chinese Medicine Key Laboratory for Metabolic Diseases,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学广东省代谢病中西医结合研究中心,广州510006 [2]广东药科大学广东省代谢性疾病中医药防治重点实验室,广州510006

出　　处：《中国新药杂志》2025年第5期511-521,共11页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81830113,82074210);广东省重大基础及应用基础研究资助项目(2019B030302005)。

摘　　要：目的:探究田黄方通过调节肠道菌群改善小鼠非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的作用及机制。方法:采用高脂饮食诱导NAFLD模型,给予阿托伐他汀和田黄方进行干预。灌胃给药8周后,收集田黄方高剂量组和模型组小鼠的新鲜粪便制作菌液进行粪菌移植实验。实验结束后,检测小鼠血脂和肝功能相关指标;采用HE染色和油红O染色分析小鼠肝脏组织病理变化;通过PCR技术检测肝组织中炎症因子、脂肪酸合成及脂肪酸β氧化相关基因的mRNA表达;采用16S rRNA测序技术分析小鼠肠道菌群的变化。结果:与模型组比较,阿托伐他汀组和田黄方低、高剂量组小鼠肝脏脂肪变性和肝损伤缓解,体重、血清血脂水平显著降低(P<0.01)。与移植对照组相比,移植田黄方菌液组小鼠肝脏脂肪变性明显改善,血清三酰甘油、肝脏谷草转氨酶水平及肝脏炎症因子、脂肪酸合成相关基因mRNA表达显著降低(P<0.05),脂肪酸β氧化相关基因mRNA表达显著升高(P<0.05)。16S rRNA测序结果显示,移植田黄方菌液组较移植对照组小鼠肠道菌群结构发生变化。在属水平上,移植田黄方菌液组拟杆菌属等有害菌丰度显著下降(P<0.05),乳酸杆菌属等有益菌丰度显著上升(P<0.05)。相关性分析表明乳酸杆菌属、拟杆菌属等与肝功能、血脂、炎症因子、脂肪酸合成及脂肪酸β氧化显著相关。结论:本研究揭示田黄方可能通过改善小鼠肠道菌群失调并影响肝脏炎症因子、脂肪酸合成以及脂肪酸β氧化,发挥对NAFLD的治疗作用。Objective:To investigate the effect and mechanism of the Tianhuang formula(TH)in improving nonalcoholic fatty liver disease(NAFLD)in mice by regulating gut microbiota.Methods:High-fat diet was used to induce a NAFLD model.After 8 weeks of oral administration of atorvastatin or TH,fresh feces from mice in the high-dose TH group and the model group were collected to prepare microbiota suspensions for fecal microbiota transplantation experiments.At the end of the experiment,blood lipid and liver function indicators in mice were examined;hematoxylin and eosin staining and oil red O staining were used to analyze pathological changes in mice liver tissue;PCR technology was utilized to detect the expressions of mRNA of inflammatory factors,fatty acid synthesis,and fatty acidβ-oxidation-related genes in liver tissues;16S rRNA sequencing was conducted to analyze changes in the gut microbiota of mice.Results:Compared with the model group,liver steatosis and liver injury were alleviated,and the body weight and serum lipid levels were significantly reduced(P<0.01)in the mice of the atorvastatin and low and high dose TH groups.Compared with the transplantation control group,significant improvement in liver steatosis,reduced levels of serum triglycerides,aspartate aminotransferase,liver inflammatory factors,and the expression of fatty acid synthesis-related gene mRNA were observed in the TH microbiota transplantation group(P<0.05),along with a significant increase in the expression of fatty acidβ-oxidation-related gene mRNA(P<0.05).The 16S rRNA sequencing results showed that the gut microbiota structure changed in the TH microbiota transplantation group compared with the transplantation control group.At the genus level,the abundance of harmful bacteria such as Bacteroides decreased significantly(P<0.05),while the abundance of beneficial bacteria such as Lactobacillus increased significantly(P<0.05)in the TH microbiota transplantation group.Correlation analysis indicated significant associations of Lactobacillus,Bacteroides,e

关 键 词：田黄方 非酒精性脂肪性肝病 肠道菌群 粪菌移植 16S rRNA 

分 类 号：R965[医药卫生—药理学]