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  

Effect of Xiaoyao Wan on endogenous metabolites in feces of rats with metabolic associated steatohepatitis

作　　者：张馨月 张玉伟 李梦琪 孟雅楠 李若瑜 苗宇船 ZHANG Xinyue;ZHANG Yuwei;LI Mengqi;MENG Yanan;LI Ruoyu;MIAO Yuchuan(Department of Pathology,Shanxi University of Chinese Medicine,Jinzhong 030619,China;Department of Encephalopathy,Shanxi University of Chinese Medicine Affiliated Hospital)

机构地区：[1]山西中医药大学病理教研室,晋中030619 [2]山西中医药大学附属医院脑病科

出　　处：《山西医科大学学报》2024年第1期36-43,共8页Journal of Shanxi Medical University

基　　金：国家自然科学基金项目(81470190);山西省卫生健康委科研课题项目(2019089);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(2021PY-JC-04)。

摘　　要：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0.3348 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 CCl 4,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[0.3348g/(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 comp

关 键 词：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 

分 类 号：R575.1[医药卫生—消化系统]