基于“土壅木郁”理论探讨益糖康调控FXR对T2DM大鼠肝糖原合成的影响  

Discussion on the effects of Yitangkang on hepatic glycogen synthesis in T2DM rats by regulating FXR based on the theory of‘earth stagnation and wood depression’

作　　者：李嘉鑫 于嘉祥 吕雪辉 刘军彤 杨宇峰[1] 石岩[1] LI Jia-xin;YU Jia-xiang;LYU Xue-hui;LIU Jun-tong;YANG Yu-feng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学,沈阳110847

出　　处：《中华中医药杂志》2023年第5期2424-2429,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：辽宁省“百千万人才工程”资助项目(No.2020921039);辽宁省“兴辽英才计划”青年拔尖人才资助项目(No.XLYC1807145)。

摘　　要：目的:基于“土壅木郁”理论观察益糖康对2型糖尿病(T2DM)大鼠FXR以及肝糖原合成的影响及作用机制。方法:96只Wistar大鼠,随机选取16只作为正常对照组,其余的80只采用高糖高脂饲料联合腹腔注射链脲佐菌素(STZ),构建T2DM大鼠胰岛素抵抗(IR)模型。按照随机数表法将造模成功大鼠分为模型对照组,益糖康高、中、低剂量组以及鹅去氧胆酸(CDCA)组,分别进行不同干预措施,连续8周。在干预前和干预后第2、4、6、8周检测空腹血糖(FPG)值。对肝脏组织进行PAS染色,观察肝糖原合成情况,运用免疫荧光法检测FXR、GSK-3β的表达情况。应用Western Blot和RT-qPCR法检测FXR、IRS1、PI3K、AKT、GSK-3β、GS相关蛋白和基因表达情况。结果:80只Wistar大鼠的建模成功率为91.25%。干预第2、4、6、8周后,与模型对照组比较,益糖康高、中、低剂量组及CDCA组FBG均显著下降(P<0.05,P<0.01)。与模型对照组比较,CDCA组及益糖康高、中、低剂量组PAS染色颜色均有不同程度变浅,其中CDCA组和益糖康高剂量组改变更加显著(P<0.01)。与模型对照组比较,益糖康高、中剂量组及CDCA组FXR、IRS1、PI3K、AKT、GS蛋白和基因均显著升高(P<0.01,P<0.05),GSK-3β蛋白和基因显著降低(P<0.01);与益糖康低剂量组比较,益糖康高剂量组和CDCA组GSK-3β蛋白和基因水平显著下降(P<0.01),其余蛋白和基因均显著升高(P<0.01,P<0.05)。结论:“土壅木郁”为T2DM关键病机,益糖康能够降低T2DM大鼠血糖,促进肝糖原合成,其作用机制与上调FXR的表达以激活PI3K/AKT/GSK-3β信号通路密切相关。Objective:To obsever the effects of Yitangkang on hepatic glycogen synthesis in T2DM rats regulating of FXR based on the theory of‘earth stagnation and wood depression’.Methods:Among 96 Wistar rats,16 were randomly selected as the normal control group,and the other 80 rats were fed high sugar and high fat diet combined with peritoneal injection of streptozotocin(STZ)to construct the IR model of T2DM rats.According to random number table method,the rats were divided into model control group,Yitangkang high-dose,medium-dose and low-dose groups,and goannedeoxycholic acid(CDCA)group,respectively,and received different interventions for 8 weeks.Fasting blood glucose(FPG)was measured before intervention and at 2,4,6,and 8 weeks after intervention.The liver tissue was stained with PAS to observe the glycogen synthesis.The expressions of FXR and GSK-3βwere detected by immunofluorescence method.The protein and mRNA expressions of FXR,IRS1,PI3K,AKT,GSK-3β,GS related proteins and genes were detected by Western Blot and RT-qPCR,respectively.Results:The modeling success rate of 80 Wistar rats was 91.25%.After 2,4,6 and 8 weeks of intervention,FBG in Yitangkang high,medium and low dose groups and CDCA group were significantly decreased compared with model control group(P<0.05,P<0.01).Compared with model control group,PAS staining color in CDCA group,Yitangkang high-dose,medium-dose and low-dose groups was lightening to varying degrees,and the change was more significant in CDCA group and high-dose group.Compared with model control group,FXR,IRS1,PI3K,AKT and GS proteins and genes in Yitangkang high-dose and medium-dose groups and CDCA groups were significantly increased(P<0.01,P<0.05),while GSK-3βproteins and genes were significantly decreased(P<0.01).Compared with low-dose group,the protein and gene levels of GSK-3βin Yitangkang high-dose group and CDCA group were significantly decreased(P<0.01),and the other proteins and genes were significantly increased(P<0.01,P<0.05).Conclusion:‘Earth stagnation and wood depress

关 键 词：土壅木郁 益糖康 2型糖尿病 肝糖原合成 FXR PI3K/AKT/GSK-3β信号通路 

分 类 号：R285.5[医药卫生—中药学]