文献类型：期刊文献

中文题名：基于AMPK/PGC-1α信号通路研究红芪多糖对糖尿病胃轻瘫大鼠胃窦组织能量代谢的影响及作用机制

英文题名：Effect and Mechanism of Hedysarum Polybotrys Saccharide on Energy Metabolism of Gastric Antrum Tissue in Diabetic Gastroparesis Rats Based on AMPK/PGC-1αSignaling Pathway

作者：何蕴良[1];万生芳[1];张磊[1];舒畅[1];李亚玲[1];李荣科[1];魏昭晖[1];郭倩[1];马欣欣[1]

第一作者：何蕴良

机构：[1]甘肃中医药大学,兰州730000

第一机构：甘肃中医药大学

年份：2021

卷号：37

期号：3

起止页码：96

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(编号:82060914、81560718);甘肃中医药大学研究生创新基金(编号:2020CX35);甘肃省中医药管理局科研课题(编号:GZK-2017-3);甘肃省中医药研究中心2020年专项开放课题(编号:zyzx-2020-zx11)。

语种：中文

中文关键词：红芪多糖;糖尿病胃轻瘫;腺苷酸活化蛋白激酶/过氧化物酶增殖物激活受体γ共激活因子1α信号通路;能量代谢

外文关键词：Hedysarum polybotrys saccharide;diabetic gastroparesis;AMP-activated protein kinase/peroxisome proliferator-activated receptorγco-activator 1αsignaling pathway;energy metabolism

摘要：目的:研究红芪多糖对糖尿病胃轻瘫(Diabetic Gastroparesis,DGP)大鼠胃窦组织能量代谢的影响,并从腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)/过氧化物酶增殖物激活受体γ共激活因子1α(peroxisome proliferator-activated receptorγco-activator 1α,PGC-1α)信号通路探讨其相关作用机制。方法:Wistar雄性大鼠采用一次性大剂量腹腔注射链脲佐菌素55 mg/kg联合高糖高脂饲料不规则喂养4 w复制DGP模型,成模大鼠随机分为模型对照组、红芪多糖30、60、120 mg/kg组,莫沙必利3.5 mg/kg组,另设正常对照组。各组分别予等体积相应药物或纯净水灌胃,每日1次,连续8 w。透射电镜观察各组大鼠胃窦组织黏膜层超微结构改变;ELISA法检测大鼠血清腺苷三磷酸(ATP)、腺嘌呤核糖核苷酸(AMP)和二磷酸腺苷(ADP)含量;Western blot检测胃窦组织中AMPK、p-AMPK、PGC-1α、沉默信息调节因子1(silent information regulator 1,SIRT1)蛋白表达变化。结果:与正常对照组比较,模型对照组血清ATP、ADP含量显著降低(P<0.01),血清AMP含量明显升高(P<0.05),胃窦组织中p-AMPK、PGC-1α、SIRT1蛋白表达显著下调(P<0.01),胃窦组织细胞核严重皱缩变形,核外仅见极少量的线粒体分布,染色体内部嵴熔解;与模型对照组比较,红芪多糖120 mg/kg组和莫沙必利3.5 mg/kg组ATP含量显著升高(P<0.01),ADP含量明显升高,AMP含量明显降低(P<0.05),p-AMPK、PGC-1α、SIRT1蛋白表达显著上调(P<0.01),胃窦组织细胞核明显恢复,核外线粒体明显增多,线粒体内部嵴损坏情况逐渐恢复。结论:红芪多糖能改善DGP大鼠胃窦组织能量代谢失衡,其作用机制可能与激活AMPK/PGC-1α信号通路,促进细胞线粒体生物合成,增加细胞供能,调节能量代谢有关。
Objective:To study the effect of Hedysarum polybotrys saccharide(HPS)on the energy metabolism of gastric antrum tissue in diabetic gastroparesis(DGP)rats,and explore its mechanism based on AMP-activated protein kinase(AMPK)/peroxisome proliferator-activated receptorγco-activator 1α(PGC-1α)signaling pathway.Methods:Wistar male rats received single high-dose(55 mg/kg)intraperitoneal injection of streptozotocin and irregularly fed on high-sugar and high-fat diet for four weeks to induce the DGP model.The rats were randomly divided into a normal control group,a model group,a mosapride(3.5 mg/kg)group,and low-(30 mg/kg),medium-(60 mg/kg),and high-dose(120 mg/kg)HPS groups.Rats in each group received an equal volume of corresponding drugs or pure water by gavage,once per day for eight weeks.The ultrastructure changes in the mucous layer of gastric antrum tissue were observed by transmission electron microscopy(TEM).The serum content of adenosine triphosphate(ATP),adenosine monophosphate(AMP),and adenosine diphosphate(ADP)was detected by the enzyme-linked immunosorbent assay(ELISA).The protein expression of AMPK,p-AMPK,PGC-1α,and silent information regulator 1(SIRT1)was detected by Western blot.Results:Compared with the normal control group,the model group showed declining serum content of ATP and ADP(P<0.01),increased serum content of AMP(P<0.05),and down-regulated protein expression of p-AMPK,PGC-1α,and SIRT1(P<0.01).Additionally,the model group displayed severely shrunken and deformed nuclei of gastric antrum tissue,a sparse distribution of mitochondria outside the nucleus,and fused internal crest of the chromosomes.Compared with the model group,the high-dose HPS group and the mosapride group exhibited elevated content of ATP and ADP(P<0.01,P<0.05),decreased AMP content(P<0.05),up-regulated protein expression of p-AMPK,PGC-1α,and SIRT1(P<0.01),restored nuclei of gastric antrum tissue,increased mitochondria outside the nucleus,and improved internal crest of mitochondria.Conclusion:HPS can improve the energy metabolism imbalance of gastric antrum tissue in DGP rats,and its mechanism may be related to the activation of the AMPK/PGC-1αsignaling pathway,promotion of mitochondrial biosynthesis,increase in cell energy supply,and regulation of energy metabolism.