辽宁中医药大学学报

目的 探讨复方加味小柴胡汤对代谢相关性脂肪性肝病（Metabolic associated fatty liver disease,MAFLD）小鼠的疗效和肠道菌群的影响。方法 雄性C57BL/J小鼠随机分成正常组、模型组、复方加味小柴胡汤低、高剂量组、易善复（多烯磷脂酰胆碱胶囊）组，每组10只。除正常组外，其余组给予高脂饲料诱导MAFLD模型并予不同剂量药物干预，共20周。检测小鼠体质量、肝湿重、肝指数；生化试剂盒检测血清天门冬氨酸氨基转氨酶（aspartate aminotransferase,AST）、丙氨酸氨基转氨酶（alanine aminotransferase,ALT）、总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-17(interleukin-17,IL-17)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、血清淀粉样蛋白A(serum amyloid A,SAA)、C-反应蛋白（C-reactive protein,CRP）含量；苏木素-伊红（hematoxylin-eosin,HE）染色观察肝脏组织形态；16S核糖体DNA(16S ribosomal DNA,16Sr DNA)基因测序分析小鼠肠道菌群变化。结果 与正常组比较，模型组小鼠体质量、肝湿重升高，肝指数下降；血清ALT、AST、TC、TG、LDL-C、HDL-C、IL-6、IL-17、TNF-α、CRP含量均升高；肝脏脂质蓄积增多，表明模型诱导成功。与模型组比较，复方加味小柴胡汤低、高剂量组和易善复组小鼠体质量、肝湿重、肝指数均降低，血清ALT、AST、TC、TG、LDL-C、HDL-C、IL-6、IL-17、TNF-α、CRP均降低，及肝组织脂肪变性程度均减轻。肠道菌群分析显示，与模型组比较，复方加味小柴胡汤能提高小鼠肠道菌群的丰富度和多样性；在门水平上，升高MAFLD小鼠的拟杆菌门和放线菌门；在属水平上，升高双歧杆菌属Bifidobacterium、乳杆菌属Lactobacillus和拟杆菌属Bacteroides＿H丰度，发挥主要作用。结论 复方加味小柴胡汤可通过减轻脂质蓄积、抑制炎症、调节肠道菌群稳态来治疗MAFLD。

Objective To explore the effect of Modified Xiaochaihu Decoction（复方加味小柴胡汤）on the intestinal flora of mice with metabolically associated fatty liver disease(MAFLD). Methods Male C57 BL/J mice were randomly divided into normal group(NC),model group(HFD),Modified Xiaochaihu Decoction low-dose group(HFD+ZFL),high-dose group(HFD+ZFH)and Polyene phosphatidylcholine group(HFD+PPC),with 10 mice in each group. Except the normal group,the other groups were given high-fat diet induced MAFLD model and different doses of drug intervention for a total of 20 weeks. Body mass,liver wet weight and liver index were detected. Detection of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),interleukin-6(IL-6),interleukin-17(IL-17)by biochemical kit,tumor necrosis factor-α(TNF-α),serum amyloid A(SAA),C-reactive protein(CRP)content;The liver morphology was observed by hematoxylin-eosin(HE)staining. 16S ribosomal DNA(16 Sr DNA)gene sequencing was used to analyze the changes of intestinal flora in mice. Results The results showed that compared with NC,the body weight and liver wet weight of mice in HFD increased,while the liver index decreased. Serum ALT,AST,TC,TG,LDL-C,HDL-C,IL-6,IL-17,TNF-α and CRP levels were increased. Liver lipid accumulation increased,indicating successful model induction. Compared with HFD,the body weight,liver wet weight and liver index of the mice in HFD+ZFL,HFD+ZFH and HFD+PPC were decreased. Serum levels of ALT,AST,TC,TG,LDL-C,HDL-C,IL-6,IL-17,TNF-α and CRP of mice in HFD+ZFL,HFD+ZFH and HFD+PPC were decreased. The degree of hepatic steatosis of mice in HFD+ZFL,HFD+ZFH and HFD+PPC were reduced. Intestinal flora analysis showed that compared with HFD,Modified Xiaochaihu Decoction could improve the richness and diversity of intestinal flora in mice. At the phylum level,Bacteroidetes and Actinomycetes were increased in MAFLD mice. At the genus level,it plays a major role in increasing the abundance of Bifidobacterium,Lactobacillus and Bacteroides＿H. Conclusion Modified Xiaochaihu Decoction can treat MAFLD by reducing lipid accumulation,inhibiting inflammation and regulating intestinal flora homeostasis.