红芪多糖对糖尿病大鼠FXR-FGF19信号通路的影响  

Effects of Hedysarum polybotrys polysacchcaide on FXR-FGF19 signal pathway in diabetes rats

作　　者：张磊 万生芳 李亚玲 梁乾坤 田一虹 马欣欣 郭倩 ZHANG Lei;WAN Sheng-fang;LI Ya-ling;LIANG Qian-kun;TIAN Yi-hong;MA Xin-xin;GUO Qian(School of Basic Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu Province,China;School of Public Health,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu Province,China;Traditional Chinese Medicine Syndrome Research Base of Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China)

机构地区：[1]甘肃中医药大学基础医学院,甘肃兰州730000 [2]甘肃中医药大学公共卫生学院,甘肃兰州730000 [3]福建中医药大学中医证研究基地,福建福州350122

出　　处：《中国临床药理学杂志》2025年第1期76-80,共5页The Chinese Journal of Clinical Pharmacology

基　　金：甘肃省高等学校青年博士基金资助项目(2022QB-096);甘肃省科技计划(自筹经费)基金资助项目(21JR1RA274);敦煌医学与转化教育部重点实验室开放课题基金资助项目(DHYX20-04)。

摘　　要：目的研究红芪多糖(HPS)对糖尿病大鼠肝组织法尼醇X受体(FXR)-成纤维细胞生长因子19(FGF19)信号通路的影响。方法Wistar雄性大鼠随机选取12只作为正常组,其余大鼠用一次性腹腔注射链脲佐菌素(50 mg·kg^(-1)STZ)联合高糖高脂饮食饲养复制糖尿病大鼠模型。成模大鼠随机分为模型组、阳性对照组(给予双歧杆菌四联活菌片混悬液400 mg·kg^(-1)·d^(-1)灌胃)和高、中、低剂量实验组(分别给予200、100、50 mg·kg^(-1)·d^(-1)HPS混悬液灌胃),正常组和模型组给予等体积纯净水灌胃,每日1次,连续8周。用血糖仪检测血糖(Glu)水平,用酶联免疫吸附试验(ELISA)试剂盒检测血清三酰甘油(TG)及总胆固醇(TC)含量,实时荧光定量聚合酶链反应法(RT-PCR)、蛋白质印迹(Western blot)法分别检测小肠组织FXR和肝组织成纤维细胞生长因子受体4(FGFR4)mRNA和蛋白相对表达水平。结果正常组、模型组、阳性对照组和高剂量实验组治疗后Glu浓度分别为(7.66±0.61)、(29.25±1.64)、(23.31±3.02)和(19.31±5.13)mmol·L^(-1),TG含量分别为(957.00±113.73)、(1345.00±246.44)、(958.00±96.53)和(964.00±130.22)μmol·L^(-1),TC含量分别为(161.65±4.53)、(302.19±5.35)、(236.09±5.14)和(165.58±2.58)μmol·L^(-1),小肠组织中FXR mRNA相对表达水平分别为1.00±0.06、0.48±0.02、0.67±0.04和0.92±0.04,肝组织中FGFR4 mRNA相对表达水平分别为1.00±0.04、0.17±0.01、0.48±0.04和0.41±0.03;模型组的上述指标与对照组比较,对照组和高剂量实验组的上述指标与模型组比价,在统计学上差异均有统计学意义(均P<0.01)。FXR和FGFR4蛋白表达结果的趋势与基因表达一致。结论HPS改善血糖、降脂、保护肝肠组织,可能是通过调控肠组织FXR-FGF19信号通路,调节胆汁酸合成实现的。Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg^(-1) STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg^(-1)·d^(-1) ssutspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg^(-1)·d^(-1) doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXRfibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Clu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L^(-1),respectively;the TG content were(957.00±113.73),(1345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L^(-1),respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L^(-1),respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model gro

关 键 词：红芪多糖 糖尿病 法尼醇X受体 胆汁酸 肝肠循环 

分 类 号：R28[医药卫生—中药学]