文献类型：期刊文献

中文题名：红芪多糖调控FXR-SHP通路改善糖尿病大鼠肝组织糖脂代谢的研究

英文题名：Study of Hedysarum polybotrys polysacchcaide regulating FXR-SHP pathway to improve glucose and lipid metabolism in liver tissue of diabetes rats

作者：张磊[1,3];万生芳[1];李亚玲[1];梁乾坤[1];田一虹[2];马欣欣[1];郭倩[1]

第一作者：张磊

机构：[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

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2024

卷号：40

期号：17

起止页码：2538

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

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)。

语种：中文

中文关键词：红芪多糖;糖尿病;法尼醇X受体;肝组织;糖脂代谢

外文关键词：Hedysarum polybotrys polysacchcaide;diabetes mellitus;farnesoid X receptor;glucose and lipid metabolism

摘要：目的探究红芪多糖(HPS)对糖尿病大鼠肝组织法尼醇X受体(FXR)-小分子异源二聚体伴侣受体(SHP)信号通路及糖脂代谢关键蛋白的影响。方法Wistar雄性大鼠随机选取12只作为空白组,其余60只采用一次性腹腔注射链脲佐菌素(STZ,50 mg·kg^(-1))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(灌胃给予双歧杆菌四联活菌片混悬液400 mg·kg^(-1)·d^(-1)),HPS高、中、低剂量实验组(分别灌胃给予HPS混悬液200、100、50 mg·kg^(-1)·d^(-1)剂量);空白组和模型组灌胃给予等体积纯净水,每日1次,连续8周。灌胃前后测血糖(Glu),用实时荧光聚合酶链反应(RT-PCR)法、蛋白质印迹(Western blot)法分别检测肝组织法尼醇X受体(FXR)、小分子异源二聚体伴侣受体(SHP)、抗过氧化物酶体增殖物激活受体α(PPARα)、抗磷酸烯醇丙酮酸羧化激酶(PEPCK)、甾醇调节原件结合蛋白-1c(SREBP-1c)、抗葡萄糖-6-磷酸酶(G6Pase)mRNA和蛋白相对表达水平。结果正常组、模型组、阳性对照组、HPS高剂量实验组治疗后Glu分别为(7.66±0.61)、(29.25±1.64)、(23.31±3.02)、(19.31±5.13)mmol·L^(-1),肝组织中FXR mRNA相对表达水平分别为1.00±0.04、0.44±0.03、0.61±0.06、0.87±0.03,SHP mRNA相对表达水平分别为1.00±0.04、0.40±0.01、0.67±0.01、0.67±0.02,肝组织中G6Pase mRNA相对表达水平分别为1.00±0.06、3.00±0.08、1.87±0.03、1.44±0.05,肝组织中PEPCK mRNA相对表达水平分别为1.00±0.04、1.88±0.03、1.31±0.02、1.23±0.04,肝组织中SREBP-1c mRNA相对表达水平分别为1.00±0.04、1.90±0.01、1.26±0.03、1.06±0.04,肝组织中PPARαmRNA相对表达水平分别为1.00±0.02、0.16±0.01、0.45±0.01、0.96±0.03;模型组的上述指标与空白组比较,阳性对照组及HPS高剂量组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.01)。FXR、SHP、G6Pase、PEPCK、SREBP-1c、PPARα蛋白表达结果的趋势与mRNA表达一致。结论HPS可能通过调控肝组织FXR-SHP信号通路,抑制糖尿病大鼠肝组织糖脂代谢关键蛋白表达,促进脂质氧化,从而改善血糖,保护肝组织。
Objective To investigate the effects of Astragalus polysaccharides(HPS)on farnitol X receptor(FXR)-small heterodimer chaperone receptor(SHP)signaling pathway and key proteins of glucose and lipid metabolism in diabetic rats.Methods Twelve male Wistar rats were randomly selected as blank group,and the remaining 60 rats were fed with a one-time intrabitoneal injection of stre pt ozotocin(STZ,50 mg·kg^(-1))combined with a high-sugar and high-fat diet to replicate the diabetic rat model.The model rats were randomly divided into model group,positive control group(400 mg·kg^(-1)·d^(-1)Bifidobacterium quadruple viable bacterial tablet suspension),experimental-H,-M,-L groups(200,100 and 50 mg·kg^(-1)·d^(-1)HPS suspension),respectively.Blank group and model group were given equal volume of pure water once a day for 8 weeks.Blood glucose(Glu)was measured before and after gavage.Real-time fluorescent polymerase chain reaction(RT-PCR),Western blot were used to detect the mRNA and protein expression level of FXR,SHP,antiperoxisomal proliferator-activated receptorα(PPARα),antiphosphoenolpyruvate carboxylkinase(PEPCK),sterol regulatory receptor binding protein-1c(SREBP-1c),glucose 6 phosphatase(G6Pase).Results Glu levels in normal group,model group,positive control group and experimental-H group after treatment were(7.66±0.61),(29.25±1.64),(23.31±3.02),(19.31±5.13)mmol·L^(-1),respectively;the relative expression levels of FXR mRNA in liver tissues were 1.00±0.04,0.44±0.03,0.61±0.06,0.87±0.03,respectively;the relative expression levels of SHP mRNA were 1.00±0.04,0.40±0.01,0.67±0.01,0.67±0.02;the relative expression levels of G6Pase mRNA in liver tissues were 1.00±0.06,3.00±0.08,1.87±0.03,1.44±0.05,respectively;the relative expression levels of PEPCK mRNA in liver tissues were 1.00±0.04,1.88±0.03,1.31±0.02,1.23±0.04,respectively;the relative expression levels of SREBP-1c mRNA in liver tissues were 1.00±0.04,1.90±0.01,1.26±0.03,1.06±0.04;the relative expression levels of PPARαmRNA in liver tissues were 1.00±0.02,0.16±0.01,0.45±0.01,0.96±0.03,respectively.Compared with blank group,positive control group and experimental-H group,there were statistically significant differences in the above indexes between model group and blank group(all P<0.01).The protein expression trend of FXR,SHP,G6Pase,PEPCK,SREBP-1c,PPARαwas consistent with mRNA expression.Conclusion HPS may regulate FXR-SHP signaling pathway in liver tissue,inhibit the expression of key proteins of glucose and lipid metabolism,promote lipid oxidation,improve Glu and protect liver tissue in diabetic rats.