摘要
目的 从粪便代谢组学和过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor alpha,PPARα)、过氧化物酶体增殖子活化受体γ共激活因子(peroxisome proliferator-activated receptor gamma coactivator,PGC)-1α探讨逍遥丸对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)大鼠的治疗作用。方法 24只雄性SD大鼠随机分为对照组、模型组、治疗组。高糖高脂饮食+四氯化碳(carbon tetrachloride,CCl4)注射4周建立NASH模型,治疗组予逍遥丸灌胃。4周后检测各组大鼠肝指数、体质量指数、血清生化指标,苏木精-伊红(hematoxylin and eosin,HE)染色和油红O染色观察肝组织病理变化,高通量液相色谱-质谱联用(liquid chromatography mass spectrometry, LC-MS)技术分析各组大鼠粪便代谢物谱,Western blot法检测各组大鼠肝组织中PPARα、PGC1α蛋白表达情况。结果 与对照组比较,模型组大鼠肝指数、血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、总胆固醇(total cholesterol,T-CHO)、甘油三酯(triglycerides,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、白介素(interleukin,IL)-1β、IL-6含量显著升高(P<0.05),体质量指数、血清IL-10含量显著下降(P<0.05),肝组织中PPARα、PGC1α蛋白表达明显降低(P<0.05)。逍遥丸对模型组大鼠上述指标均有明显的调节作用(P<0.05),且能够显著改善肝组织病理。与对照组比较,模型组大鼠有57种代谢物发生了明显变化,其中乙酰左旋肉碱、组胺、丙酮酸、L-丝氨酸、胞嘧啶等25种代谢物在逍遥丸干预后明显改善(P<0.05),涉及组氨酸代谢、精氨酸生物合成、嘌呤代谢、半胱氨酸与蛋氨酸代谢和苯丙氨酸代谢等5条代谢通路。结论 逍遥丸可通过上调PPARα、PGC1α在NASH大鼠肝组织中的表达来诱导脂肪酸β氧化,并通过改善粪便代谢物谱、减轻脂肪在肝细胞内堆积,起到治疗NASH的作用。
Objective From the aspects of fecal metabolomics and peroxisome proliferator-activated receptor alpha(PPARα),peroxisome proliferator-activated receptor gamma coactivator(PGC)1αto research the therapeutic effect of Xiaoyao Pill on nonalcoholic steatohepatitis(NASH)rats.Methods 24 male SD rats were randomly divided into control,model,and treatment groups.The rat model of NASH was established by high-sugar and high-fat diet and subcutaneous injection of carbon tetrachloride(CCl 4)for 4 weeks,and the treatment group was given Xiaoyao Pill by gavage.After 4 weeks,the liver index,body mass index,and serum biochemical indexes of the rats in each group were detected,and the pathological changes of liver tissue were observed by hematoxylin and eosin(HE)staining and Oil Red O staining.Liquid chromatography mass spectrometry(LC-MS)was used to analyze the fecal metabolite profiles of rats.Western blot was used to detect the expressions of PPARαand PGC-1αproteins in the liver tissues of rats.Results Compared with the control group,the liver index,serum ALT,T-CHO,TG,LDL-C,interleukin(IL)-1β,and IL-6 were significantly increased(P<0.05),while body mass index and serum IL-10 significantly decreased(P<0.05)in model group rats.The protein expressions of PPARαand PGC1αin liver tissue were significantly decreased(P<0.05)in model group rats.Xiaoyao Pill had obvious regulating effects on the above indicators(P<0.05),and significantly improved the pathology of liver tissue.Compared with the control group,57 metabolites in the model group were significantly changed,among which 25 metabolites including acetyl-L-carnitine,histamine,pyruvate,L-serine,cytosine were significantly improved after Xiaoyao Pill intervention(P<0.05),involving 5 metabolic pathways including histidine metabolism,arginine biosynthesis,purine metabolism,cysteine and methionine metabolism,and phenylalanine metabolism.Conclusion Xiaoyao Pill can up-regulate the expression of PPARα,PGC1αin the liver tissue of NASH rats,induce fatty acidβ-oxidation,improve the fecal metabolite profile,reduce the accumulation of fat in hepatocytes,and relieve NASH.
作者
张玉伟
孟雅楠
张馨月
苗宇船
ZHANG Yuwei;MENG Yanan;ZHANG Xinyue;MIAO Yuchuan(Shanxi Academy of Traditional Chinese Medicine,Taiyuan 030000,China;Shanxi University of Chinese Medicine,Jinzhong 030619,China)
出处
《中国中医基础医学杂志》
CAS
CSCD
北大核心
2023年第11期1829-1834,共6页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家自然科学基金项目(81470190)
山西省卫生健康委项目(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)。
作者简介
张玉伟(1990-),女,在读硕士研究生,从事肝病的病因病机及中医药防治研究;通讯作者:苗宇船(1965-),女,硕士研究生导师,从事肝病的病因病机及中医药防治研究,E-mail:mych65@163.com。
