六味降脂汤对高脂血症大鼠肠道菌群及小肠NPC1L 1、ACAT2和APOB48蛋白表达的影响  

Liuwei Jiangzhi Decoction(六味降脂汤)Affects Intestinal Flora and Expression of NPC1L1,ACAT2,and APOB48 in Small Intestine of Hyperlipidemia Rats

作　　者：杜京晏 张远哲 蔡琨 谢珂 全德森 田维毅 黎豫川 DU Jingyan;ZHANG Yuanzhe;CAI Kun;XIE Ke;QUAN Desen;TIAN Weiyi;LI Yuchuan(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025;Department of Pharmacy,Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550025)

机构地区：[1]贵州中医药大学基础医学院,贵阳550025 [2]贵州中医药大学第二附属医院药学部,贵阳550025

出　　处：《中药药理与临床》2023年第6期23-30,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：贵阳市科技计划项目(筑科合同[2019]-9-4-19);贵州中医药大学博士基金项目([2019]25号、[2019]22号);贵州中医药大学第二附属医院院内科研项目(GZEYK[2020]7号)。

摘　　要：目的:探究六味降脂汤对高脂血症可能的干预机制以及对肠道菌群的影响。方法:60只SPF级SD雄性大鼠随机分为正常对照组、模型对照组、阿托伐他汀0.9 mg/kg组及六味降脂汤5.4、10.7、21.4 g/kg。除正常对照组外,其余各组给予高脂饲料合并高脂乳剂灌胃6 w制备高脂血症大鼠模型,造模成功各组灌胃给予相应药物,8 w后采集血清、粪便及小肠组织样本,检测大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)含量;同时采用16S rDNA高通量测序分析肠道菌群的多样性和结构变化;免疫组织化学法检测大鼠小肠组织NPC1L1、ACAT2及APOB48蛋白表达。结果:与正常对照组比较,模型对照组大鼠血清TC、TG、LDL-C含量显著升高,小肠NPC1L1、ACAT2及APOB48蛋白表达显著上调(P<0.01),肠道菌群Beta多样性改变;与模型对照组比较,各给药组TC、TG、LDL-C含量均明显降低(P<0.05或P<0.01),六味降脂汤10.7 g/kg组小肠NPC1L1、ACAT2及APOB48蛋白表达明显下调(P<0.05或P<0.01),肠道菌群结构改变,在门水平上,厚壁菌门(Firmicutes)相对丰度明显降低,拟杆菌门(Bacteroidetes)相对丰度明显升高(P<0.05或P<0.01);属水平上,布劳特氏菌属(Blautia)相对丰度明显升高,乳杆菌属(Lactobacillus)及Ruthenibacterium相对丰度明显降低(P<0.05或P<0.01)。结论:六味降脂汤可能通过下调小肠NPC1L1、ACAT2和APOB48蛋白的表达,影响肠道微生物群,调节高脂血症大鼠体内脂质代谢,从而达到降脂作用。Objective:To explore the mechanism of Liuwei Jiangzhi Decoction(六味降脂汤)in the treatment of hyperlipidemia from intestinal flora.Methods:Sixty SPF-grade SD male rats were randomly assigned into a blank control group,a model group,an atorvastatin(0.9 mg/kg)group,and Liuwei Jiangzhi Decoction(5.4,10.7,and 21.4 g/kg)groups.The rat model of hyperlipidemia was established in other groups except the blank control by feeding with a high-fat diet and a high-fat emulsion for 6 weeks.After successful modeling,the rats were administrated with corresponding drugs for 8 weeks,and then the samples of serum,feces and intestinal tissue were collected.The serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were determined.The 16S rDNA high-throughput sequencing was employed to analyze the diversity and structural changes of the intestinal flora,and immunohistochemistry(IHC)to determine the expression of Niemann-Pick C1-like 1(NPC1L1),acyl coenzyme A:cholesterol acyltransferase 2(ACAT2),and apolipoprotein B-48(APOB48)in the small intestine.Results:Compared with the blank control group,the model group showed elevated serum levels of TC,TG,and LDL-C,up-regulated expression levels of NPC1L1,ACAT2,and APOB48 in the small intestine(P<0.01),and changed beta diversity of intestinal flora.Compared with the model group,the drug intervention lowered the serum levels of TC,TG and LDL-C(P<0.05 or P<0.01),and 10.7 g/kg Liuwei Jiangzhi Decoction showed the best effect and down-regulated the protein levels of NPC1L1,ACAT2,and APOB48 in the small intestine(P<0.05 or P<0.01).Moreover,this group changed the structure of intestinal flora.Specifically,the intervention decreased the relative abundance of Firmicutes and increased the relative abundance of Bacteroidetes at the phylum level,and decreased the relative abundance of Lactobacillus and Ruthenibacterium and increased the relative abundance of Blautia at the genus level.Conclusion:Liuwei Jiangzhi

关 键 词：六味降脂汤 高脂血症 肠道菌群 尼曼-匹克C1型类似蛋白1 酰基辅酶A-胆固醇酰基转移酶2 载脂蛋白B48 

分 类 号：R285.5[医药卫生—中药学]