基于“肠道菌群-甘油磷脂代谢-巨噬细胞极化”途径探讨黄蜀葵花总黄酮治疗溃疡性结肠炎与抑郁共病机制  

Mechanism of total flavone of Abelmoschus manihot in treating ulcerative colitis and depression via intestinal flora-glycerophospholipid metabolism-macrophage polarization pathway

作　　者：陆长叶 袁晓敏 何林海 冒佳蓉 陈玉根[1] LU Chang-ye;YUAN Xiao-min;HE Lin-hai;MAO Jia-rong;CHEN Yu-gen(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Nursing School of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院,江苏南京210029 [2]南京中医药大学护理学院,江苏南京210029

出　　处：《中国中药杂志》2025年第5期1286-1297,共12页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82174379);国家自然科学基金青年基金项目(82405401);江苏省自然科学基金青年项目(BK20240744);江苏省研究生科研与实践创新计划项目(SJCX24_0971)。

摘　　要：探讨黄蜀葵花总黄酮(TFA)通过调控肠道菌群重塑甘油磷脂代谢,进而抑制巨噬细胞M1极化治疗溃疡性结肠炎(UC)与抑郁共病的作用机制。建立慢性束缚应激(CRS)与葡聚糖硫酸钠(DSS)诱导的UC抑郁共病小鼠模型。采用TFA干预后的粪菌移植(FMT)实验,FMT供体组小鼠经造模及给药后取粪便制备菌液,FMT受体组小鼠经抗生素干预后予供体组菌液灌胃,继而进行UC抑郁造模。实验结束后,进行行为学测试,并检测小鼠脑海马组织中5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)水平评估抑郁样行为,检测小鼠脑、结肠组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平,检测CD86、CD206 mRNA水平评估巨噬细胞极化状态;采用16S核糖体RNA(16S rRNA)测序技术分析小鼠肠道菌群变化;广靶脂质组学检测FMT后小鼠血清脂质水平,将TFA显著调节的差异肠道微生物与脂质做关联分析;体外实验中,使用代表性甘油磷脂代谢物及甘油磷脂抑制剂干预Raw264.7巨噬细胞,检测TNF-α、IL-6、IL-1β、CD86、CD206 mRNA水平。结果显示,TFA及其干预后的FMT可明显改善UC抑郁共病小鼠抑郁样行为及肠道炎症,明显下调脑、结肠组织促炎细胞因子及明显下调脑、结肠组织促炎细胞因子及CD86 mRNA表达,抑制巨噬细胞M1极化,显著上调CD206 mRNA表达,促进巨噬细胞M2极化,高剂量组效果更加显著。TFA干预后的FMT显著纠正了UC抑郁共病小鼠甘油磷脂代谢紊乱,差异肠道菌群与甘油磷脂存在显著相关性。体外实验显示,甘油磷脂代谢物尤其是溶血磷脂酰胆碱(LPC),显著上调促炎细胞因子及CD86 mRNA表达,促进巨噬细胞M1极化,甘油磷脂抑制剂效果反之。结果表明,TFA通过纠正肠道菌群紊乱重塑甘油磷脂代谢,进而抑制巨噬细胞M1极化,有效治疗UC抑郁共病。This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA)in treating ulcerative colitis(UC)and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism.The study established a mouse model of UC and depression induced by chronic restraint stress(CRS)and dextran sulfate sodium(DSS).The fecal microbiota transplantation(FMT)experiment after TFA intervention was conducted.Mice in the FMT donor group were modeled and treated,and fecal samples were taken to prepare the bacterial solution.Mice in the FMT receptor group were treated with antibiotic intervention,and then administered bacterial solution by gavage from mice in the donor group,followed by UC depression modeling.After the experiment,behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT)and brain-derived neurotrophic factor(BDNF)in the hippocampus of mice.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured,and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206.16S ribosomal RNA(16S rRNA)sequencing technology was used to analyze changes in the intestinal flora of mice.Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA.In vitro experiments,representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages,and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected.The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression,significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue,inhi

关 键 词：黄蜀葵花总黄酮 肠道菌群 甘油磷脂代谢 巨噬细胞极化 溃疡性结肠炎与抑郁共病 

分 类 号：R285.5[医药卫生—中药学]