连翘叶改善肥胖大鼠炎症因子水平及肠道菌群结构的作用  

Effects of forsythia leaves on the levels of inflammatory factors and the structure of intestinal flora in obese rats

作　　者：田真 王紫玉 渠鹏霞 马晶鑫 李元宾 TIAN Zhen;WANG Ziyu;QU Pengxia;MA Jingxin;LI Yuanbin(Shanxi University of Chinese Medicine,Jinzhong 030602,China;Department of Endocrinology,Taiyuan Central Hospital,Taiyuan 030009,China;Department of Endocrinology,The Third People's Hospital of longgang District,Shenzhen 518112,China)

机构地区：[1]山西中医药大学第三临床学院,山西晋中030619 [2]太原市中心医院内分泌科,山西太原030009 [3]深圳市龙岗区第三人民医院内分泌科,广东深圳518112

出　　处：《海南医学院学报》2024年第13期970-981,共12页Journal of Hainan Medical University

基　　金：山西省卫生健康委科研课题[晋卫办科教函(2022)4号2022084];太原市科学技术局,国家区域医疗中心科技创新计划项目(202236)。

摘　　要：目的:观察连翘叶改善肥胖大鼠的作用,并结合炎症因子水平、肠道菌群结构分析其作用机制。方法:40只SPF级SD雄性大鼠,按体重随机分成空白组(8只)和造模组(32只),空白组给予普通饲料喂养,造模组给予高脂饲料喂养。喂养9周后,淘汰造模未成功的大鼠,最终确定模型组及连翘叶治疗组,每组各8只。连翘叶治疗组给予连翘叶冻干粉0.067 g·kg^(-1)·d^(-1)灌胃,空白组、模型组给予同等剂量生理盐水灌胃,持续10周。干预结束后,称量大鼠体重、肝脏重量、内脏脂肪重量并测量体长,计算肥胖指数、脂肪系数、肝脏系数;酶联免疫吸附法检测血清TNF‑α、IL‑6、LPS水平;苏木素‑伊红染色观察肝脏和结肠病理变化;油红O染色观察肝脏脂质沉积情况;免疫组化检测结肠claudin‑1、occludin、ZO‑1蛋白表达;宏基因组测序技术分析肠道菌群结构及功能。结果:与肥胖模型组比较,连翘叶治疗组大鼠体重及给药前后体重增加均降低(P<0.05),肥胖指数、脂肪系数、肝脏系数均降低(P<0.05),血清TNF‑α、IL‑6、LPS水平均降低(P<0.05),肝脏内脂滴空泡及脂质沉积减少,结肠绒毛结构紊乱得到改善,结肠紧密连接蛋白claudin‑1、ZO‑1表达增加(P<0.05),肠道菌群丰富度及多样性均增加(P<0.05),门水平上,梭菌门相对丰度增加(P<0.05),属水平上,普雷沃氏菌属、Pseudoflavonifractor相对丰度增加(P<0.05),萨特氏菌属、布劳特氏菌属、真杆菌属相对丰度降低(P<0.05),肠道菌群功能在DNA损伤修复中表达增加、氨基酸代谢紊乱得到改善。结论:连翘叶可能通过改善肠道菌群结构,减少肠道屏障通透性,进而减少血清炎症水平起到改善肥胖症的作用。Objective:To observe the effect of forsythia leaves on inflammatory factor levels in obese rats and the structure of the intestinal flora and the analysis of its action mechanism.Methods:Forty SPF‑grade SD male rats were randomly divided into blank group(n=8)and model group(n=32)according to body weight.The blank group was fed with normal diet,and the model group was fed with high‑fat diet.After nine weeks of feeding,the rats that failed to establish the model were finally determined as the model group and forsythia leaf treatment group,with eight rats in each group.The forsythia leaf treatment group was given forsythia leaf freeze‑dried powder 0.067 g·kg^(-1)·d^(-1) by gavage,and the blank group and the model group were given the same dose of normal saline by gavage for 10 weeks.At the end of the intervention,the body weight,liver weight,visceral fat weight and body length were measured,and the obesity index,fat coefficient and liver coefficient were calculated.The serum levels of tumor necrosis factor‑α(TNF‑α),interleukin‑6(IL‑6)and lipopolysaccharide(LPS)were detected by ELISA.Hematoxylin and eosin(HE)staining was used to observe the pathological changes of liver and colon.Oil red O staining was used to observe liver lipid deposition.Immunohistochemistry was used to detect the protein expression of claudin‑1,occludin and ZO‑1 in colon.Metagenomic sequencing technology was used to analyze the structure and function of intestinal flora.Results:Compared with the model group,the body weight and weight gain before and after administration in the forsythe leaf treatment group were decreased(P<0.05),the adiposity index,fat coefficient and liver coefficient were decreased(P<0.05),and the serum TNF‑α,IL‑6 and LPS levels were decreased(P<0.05).The expression of tight junction proteins claudin‑1 and ZO‑1 in the colon was increased(P<0.05),and the richness and diversity of intestinal flora were increased(P<0.05).At the phylum level,the relative abundance of Fusobacteria was increased(P<0.05)

关 键 词：肥胖 连翘叶 肠道菌群 炎症因子 宏基因组测序技术 

分 类 号：R285.5[医药卫生—中药学]