世界科学技术-中医药现代化2025，Vol.27Issue(10)：2851-2863,13.DOI:10.11842/wst.20250216003
基于代谢组学探讨利胆化痰活血方改善肥胖大鼠认知功能受损的作用机制
Metabolomics Insights into Lidan Huatan Huoxue Decoction Improving Cognitive Impairment in Obese Rats
摘要
Abstract
Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.关键词
利胆化痰活血方/肥胖/认知受损/代谢组学Key words
Lidan Huatan Huoxue Decoction/Obesity/Cognitive impairment/Metabolomics分类
医药卫生引用本文复制引用
张扬,吕佳璐,肖铁刚,尚浩南,赵月双,杜翔宇,徐俊,王兵..基于代谢组学探讨利胆化痰活血方改善肥胖大鼠认知功能受损的作用机制[J].世界科学技术-中医药现代化,2025,27(10):2851-2863,13.基金项目
上海市科学技术委员会自然科学基金项目(23ZR1448400):基于"少阳枢机不利"理论的利胆化痰活血方调节胆汁酸肠肝循环防治代谢综合征的机制研究,负责人:王兵 （23ZR1448400）
上海市卫生健康委员会、上海市中医药管理局项目(2024BJ003):柴胡人参药对通过改善脂肪衰老相关分泌表型(SASP)防治认知功能减退的机制研究,负责人:徐俊 （2024BJ003）
上海市卫生健康委员会中医药科研项目(2024QN076):运用粪菌移植和宏基因组学探讨利胆化痰活血方通过肠道菌群-胆汁酸轴防治代谢综合征的机制,负责人:尚浩南. （2024QN076）
