机构地区:[1]上海中医药大学附属曙光医院肝病研究所,上海201203 [2]上海中医药大学肝病研究所,上海201203 [3]上海中医药大学教育部肝肾疾病重点实验室,上海201203 [4]上海市中医临床重点实验室,上海201203
出 处:《上海中医药杂志》2024年第8期62-71,共10页Shanghai Journal of Traditional Chinese Medicine
基 金:国家自然科学基金项目(81673750);上海中医药大学附属曙光医院四明学者基金项目(SGXZ-201911)。
摘 要:目的观察血府逐瘀汤及其提取部位对高脂饮食诱导的代谢相关脂肪性肝病(MAFLD)小鼠肝脏代谢物的影响。方法将48只C57BL/6J雄性小鼠随机分为正常组,模型组,血府逐瘀汤提取部位1、2、3组及血府逐瘀汤组,每组8只。正常组予对照饲料,其余各组均予高脂饲料。造模第13周开始予灌胃相应药物,正常组和模型组灌胃等量灭菌水,16周末取材。检测小鼠肝组织三酰甘油(TG)、血清丙氨酸转氨酶(ALT),苏木精-伊红(HE)染色观察肝组织病理并定量检测肝组织代谢物。结果(1)与模型组比较,血府逐瘀汤及其各提取部位可有效改善高脂饮食诱导的MAFLD小鼠肝组织病理、血清ALT和肝脏TG(P<0.05)。(2)共定量检测到17个种类、212个代谢物。提取部位1调节9个代谢标志物,富集代谢通路16条;提取部位2调节18个代谢标志物,富集代谢通路38条;提取部位3调节18个代谢标志物,富集代谢通路25条;血府逐瘀汤调节13个代谢标志物,富集代谢通路11条。其中,血府逐瘀汤及各提取部位共同调节色氨酸及其代谢;各提取部位共同调节酪氨酸及其代谢;提取部位1特异性调节鹅去氧胆酸代谢;提取部位2特异性调节甘氨酸代谢;提取部位3特异性调节葡萄糖醛酸代谢;血府逐瘀汤特异性调节二十碳五烯酸代谢。结论血府逐瘀汤及其各提取部位在显著改善高脂饮食诱导的MAFLD的同时,对于肝脏代谢的调节既有共性,亦有各自的特点,值得深入研究。Objective To observe the effects of Xuefu Zhuyu Decoction(XZD)and its fractions on liver metabolites in mice with high-fat dietinduced metabolic associated fatty liver disease(MAFLD).Methods Forty-eight male C57BL/6J mice were randomly divided into six groups:normal group,model group,XZD fraction 1,2,and 3 groups,and XZD group,with 8 mice in each group.The mice in the normal group were given a control diet,while the mice in other groups were given a high-fat diet.Starting from the 13th week of modeling,the corresponding drugs were administered via gavage,with the mice in the normal and model groups receiving the same volume of sterile water.Samples were collected at the end of the 16th week.Liver tissue triglycerides(TG),serum alanine aminotransferase(ALT),and liver tissue metabolites were detected quantitatively,and liver tissue histopathology was observed with hematoxylin-eosin(HE)staining.Results①XZD and its fractions significantly improved liver tissue histopathology,serum ALT,and liver TG in mice with high-fat dietinduced MAFLD(P<0.05).②A total of 17 categories and 212 metabolites were quantitatively detected.Fraction 1 regulated 9 metabolic biomarkers and enriched 16 metabolic pathways.Fraction 2 regulated 18 metabolic biomarkers and enriched 38 metabolic pathways.Fraction 3 regulated 18 metabolic biomarkers and enriched 25 metabolic pathways.XZD regulated 13 metabolic biomarkers and enriched 11 metabolic pathways.Among these,XZD and its fractions collectively regulated tryptophan and its metabolism.All fractions collectively regulated tyrosine and its metabolism.Fraction 1 specifically regulated chenodeoxycholic acid metabolism,fraction 2 specifically regulated glycine metabolism,fraction 3 specifically regulated glucuronic acid metabolism,and XZD specifically regulated eicosapentaenoic acid metabolism.Conclusions XZD and its fractions significantly improved high-fat diet-induced MAFLD.The regulation of liver metabolism by XZD and its fractions shows both common and unique characteristics,meriting furt
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