基于肠肝轴探讨加味消脂利肝方调控肠道菌群治疗非酒精性脂肪肝病的作用机制  

The efficacy and mechanism of Jiawei Xiaozhi Ligan Decoction in intervention of NAFLD based on gut-liver axis

作　　者：廖小妹 陈美丽 张露 王玺舜 唐博翔 何文智[1,2] LIAO Xiaomei;CHEN Meili;ZHANG Lu;WANG Xishun;TANG Boxiang;HE Wenzhi(Stomatological College,Hu'nan University of Chinese Medicine,Changsha,Hu'nan 410218,China)

机构地区：[1]湖南中医药大学口腔医学院,湖南长沙410218 [2]湖南中医药大学 [3]湖南中医药大学附属长沙市中医医院

出　　处：《中国微生态学杂志》2023年第8期876-884,共9页Chinese Journal of Microecology

基　　金：湖南省卫健委(D202308018795);湖南中医药大学校级科研课题(2021YF08,2021dj04)。

摘　　要：目的 通过肠肝轴探讨加味消脂利肝方(简称消脂方)治疗非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)的作用机制及对肠道菌群的影响。方法 按雌雄随机将28只SD大鼠分为空白组、模型组、消脂方组和阳性对照组,模型组10只,其余每组6只。适应性饲养后,通过高脂饲料诱导法(high-fat feed,HFD)建立SD大鼠NAFLD模型。持续6周后,模型组用等体积生理盐水3.0 mL/kg灌胃,消脂方组给予消脂方7.8 g/kg灌胃,阳性对照组给予辛伐他汀0.15 mg/kg灌胃,实验持续2周,同时给予高脂饲料。实验结束后检测血清转氨酶(ALT、AST)、血脂(TG、TC、HDL-C、LDL-C)水平,并进行肝组织病理学(油红O染色)观察及肠道内容物16S rDNA高通量测序。结果 各组大鼠血清TG、TC、LDL-C、HDL-C、ALT、AST水平差异均有统计学意义(F=17.864,P<0.001;H=13.078,P=0.004;H=13.508,P=0.004;H=13.132,P=0.004;F=19.565,P=0.004;H=13.049,P=0.005)。与空白组相比,模型组大鼠血清TG、TC、LDL-C、ALT、AST水平均显著升高(P<0.001、P=0.011、P=0.005、P<0.001、P=0.012),HDL-C水平显著降低(P=0.010),肝组织脂质沉积增加(P=0.028),肠道微生物丰富度及多样性降低(P=0.014)。与模型组相比,消脂方组NAFLD大鼠血清TG、TC、LDL-C、ALT、AST水平均显著降低(P<0.001、P=0.031、P=0.042、P<0.001、P=0.029),HDL-C水平显著升高(P=0.020),同时改变肠道内容物中菌群的多样性(P=0.026),调节菌群的相对丰度。结论 消脂方通过肠肝轴调控肠道菌群丰富度及多样性,调节血脂异常改善肝损伤,从而抑制NAFLD的发生发展。Objective To explore the mechanism of Jiawei Xiaozhi Ligan Decoction(XZF)in the treatment of NAFLD in rats and the correlation between the changes and abnormal diversity and proportions of intestinal microbiota.Methods A total of 28 SD rats were randomly divided into control group,model group,XZF group and positive control group according to mouse gender.After adaptive feeding,the NAFLD SD rat models were established with high fat diet(HFD).After 6 weeks,the model group was gavaged with an equal volume of normal saline 3.0 mL/kg,the XZF group was given XZF 7.8 g/kg by gavage,and the positive control group was given simvastatin 0.15 mg/kg by gavage.The experiment lasted for 2 weeks while high-fat feed was given.After the end of the experiment,serum aminotransferases(ALT,AST),blood lipid(TG,TC,HDL-C,LDL-C),liver histopathology(oil red O staining),and intestinal content 16S rDNA high-throughput sequencing were detected.Results The TG,TC,LDL-C,HDL-C ALT and AST were statistically different among groups(F=17.864,P<0.001;H=13.078,P=0.004;H=13.508,P=0.004;H=13.132,P=0.004;F=19.565,P=0.004;H=13.049,P=0.005).Compared with the control group,the serum concentrations of TG,TC,LDL-C,ALT and AST(P<0.001,P=0.011,P=0.005,P<0.001,P=0.012)in the model group significantly increased,that of HDL-C significantly reduced(P=0.010),lipid deposition in liver tissue increased(P=0.028),and the richness and diversity of intestinal microbiota reduced(P=0.014),all of which were statistically significant.Compared to model group,XZF significantly reduced the serum levels of ALT,TG,TC and LDL-C in NAFLD rats(P<0.001,P=0.031,P=0.042,P<0.001,P=0.029),increased the level of HDL-C(P=0.020),changed the diversity of flora in intestinal contents(P=0.026),and regulated the relative abundance of colonies.Conclusion Jiawei Xiaozhi Ligan Decoction inhibits the occurrence and development of NAFLD by increasing the richness and diversity of intestinal microbiota,regulating dyslipidemia and improving liver damage.

关 键 词：肠肝轴 加味消脂利肝方 非酒精性脂肪肝病 16S rDNA高通量测序 肠道菌群 

分 类 号：R259[医药卫生—中西医结合]