首页|逍遥丸对代谢相关脂肪性肝炎大鼠粪便内源性代谢产物的影响

逍遥丸对代谢相关脂肪性肝炎大鼠粪便内源性代谢产物的影响

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目的 运用代谢组学技术研究逍遥丸对代谢相关脂肪性肝炎大鼠的疗效及其机制.方法24只SD雄性大鼠随机分为3组:对照组、模型组和逍遥丸组(XYW组).模型组和XYW组给予高脂饮食、背部皮下注射四氯化碳、饥饱失常和夹尾联合刺激4周建立代谢相关脂肪性肝炎模型,造模成功后,XYW组给予逍遥丸水溶液0.334 8 g/(kg·d),给药4周.造模和给药期间,观察大鼠一般情况.给药结束后检测不同组别大鼠的血清生化指标总胆固醇(T-CHO)、甘油三酯(TG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、低密度脂蛋白胆固醇(LDL-C)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD).运用苏木素-伊红(HE)染色法对大鼠肝组织进行病理切片观察.运用核磁共振氢谱技术测定大鼠粪便代谢产物.结果 模型组大鼠毛发晦暗、易惹怒,情绪低落、无精打采、动作迟缓、胃口不佳、排便稀溏;与模型组相比,XYW组大鼠的一般情况有显著改善.与对照组相比,模型组大鼠血清中T-CHO、TG、ALT、AST、LDL-C、MCP-1、TNF-α、IL-6水平显著升高(均P<0.05),IL-10水平显著降低(P<0.05);与模型组相比,XYW组大鼠T-CHO、TG、ALT、AST、LDL-C、MCP-1、TNF-α、IL-6水平显著降低(均P<0.05),IL-10水平显著上升(P<0.05).与对照组相比,模型组大鼠MDA水平显著升高(P<0.01),SOD水平显著降低(P<0.01);与模型组相比,XYW组大鼠MDA水平显著降低(P<0.01),SOD水平显著上升(P<0.01).HE染色结果显示,与对照组相比,模型组肝脏脂肪空泡及炎性细胞浸润增多;与模型组相比,XYW组肝脏脂肪空泡及炎性细胞浸润减少.代谢组学结果显示,与对照组相比,模型组粪便中次黄嘌呤、D-葡萄糖、N-乙酰糖蛋白、丙酸、亮氨酸、酪氨酸、胆碱、甲酸、D-木糖、苏氨酸代谢物水平发生显著变化(均P<0.05),包括苯丙氨酸、酪氨酸和色氨酸的生物合成,酪氨酸代谢等多种代谢途径;与模型组相比,XYW组粪便中次黄嘌呤、D-葡萄糖、N-乙酰糖蛋白、丙酸、亮氨酸、酪氨酸、胆碱、甲酸、D-木糖、苏氨酸代谢物水平出现显著回调(均P<0.05).结论 逍遥丸能够通过改善氨基酸代谢、脂质代谢、糖代谢紊乱,减轻氧化应激和炎症损伤保护肝细胞,改善代谢相关脂肪性肝炎.
Effect of Xiaoyao Wan on endogenous metabolites in feces of rats with metabolic associated steatohepatitis
Objective To explore the effect and its mechanism of Xiaoyao Wan on metabolic associated steatohepatitis in rats using metabolomics technology.Methods Twenty-four SD male rats were randomly divided into three groups:control group,model group and Xiaoyao Wan group(XYW group).The rats in model group and XYW group were given high-fat diet,subcutaneous injection of CCl4,hunger and satiety disorder,and tail clamping stimulation to establish the model of metabolic associated steatohepatitis for four weeks.After successful modeling,the rats in XYW group were given Xiaoyao Wan water solution[0.334 8g/(kg· d)]for four weeks.During this period,the general status of rats was observed.Serum biochemical indexes,T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α,IL-6,IL-10,and oxidative stress indicators MDA and SOD were detected in rats after administration in different groups.Patho-logical changes of liver tissues were stained with HE.Faecal metabolites in rats were analyzed using 1H-NMR.Results Rats in model group had darker hair,and were more likely to be irritated,depressed and listless,with slow movements,poorer appetite and looser defecation.The general status of rats in XYW group was significantly improved compared with model group.Compared with control group,the serum levels of T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α and IL-6 in model group were significantly increased(all P<0.05),while the level of IL-10 was significantly decreased(P<0.05).Compared with model group,the levels of T-CHO,TG,ALT,AST,LDL-C,MCP-1,TNF-α and IL-6 were significantly decreased(all P<0.05),while the level of IL-10 was significantly increased in XYW group(P<0.05).Compared with control group,the MDA level was significantly increased in model group(P<0.01),while the SOD level was significantly decreased(P<0.01).Compared with model group,the MDA level was significantly decreased in XYW group(P<0.01),while SOD level was significantly increased(P<0.01).HE staining results showed an increase in hepatic fat vacuoles and inflammatory cell infiltration in model group compared with control group.Compared with model group,liver fat vacuoles and inflammatory cell infiltration were decreased in XYW group.Metabonomics results showed significant changes in the levels of hypoxanthine,D-glucose,N-acetylglycoprotein,propionic acid,leucine,tyrosine,choline,formic acid,D-xylose and threonine metabolites in the faeces in model group compared with control group(all P<0.05),including the biosynthesis of phenylalanine,tyrosine and tryptophan,and the metabolism of tyrosine in various metabolic pathways.Compared with model group,the levels of hypoxanthine,D-glucose,N-acetylglycoprotein,propionic acid,leucine,tyrosine,choline,formic acid,D-xylose and threonine metabolites in the faeces in XYW group showed a significant regression(all P<0.05).Conclusion Xiaoyao Wan can protect hepatocytes by improving amino acid metabolism and lipid metabolism,and reducing glucose metabolism disorder,oxidative stress and inflammatory damage,thus improving the metabolic associated steatohepatitis.

Xiaoyao Wanmetabolic associated steatohepatitis(MASH)1 H nuclear magnetic resonance(1 H-NMR)fecalmetabolomics

张馨月、张玉伟、李梦琪、孟雅楠、李若瑜、苗宇船

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山西中医药大学病理教研室,晋中 030619

山西中医药大学附属医院脑病科

逍遥丸 代谢相关脂肪性肝炎 核磁共振氢谱(1H-NMR) 粪便 代谢组学

国家自然科学基金项目山西省卫生健康委科研课题项目山西中医药大学科技创新能力培育计划"基础研究专项"项目

8147019020190892021PY-JC-04

2024

山西医科大学学报
山西医科大学

山西医科大学学报

CSTPCD
影响因子:0.931
ISSN:1007-6611
年,卷(期):2024.55(1)
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