基于短链脂肪酸受体通路探讨逍遥散调节慢性应激大鼠糖代谢异常机制  

Exploration on the mechanism of Xiaoyaosan in regulating glucose metabolism abnormalities in chronic stress rats based on the short chain fatty acid receptor pathway

作　　者：李红红 王浩 崔子龙 王少贤 赵润生 张碧涛 李媛媛 范培健 LI Honghong;WANG Hao;CUI Zilong;WANG Shaoxian;ZHAO Runsheng;ZHANG Bitao;LI Yuanyuan;FAN Peijian(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Provincial Key Laboratory of Integrated Chinese and Western Medicine for Lung Disease Research,Shijiazhuang 050091,China)

机构地区：[1]河北中医药大学,石家庄050200 [2]河北省中西医结合肺病研究重点实验室,石家庄050091

出　　处：《中华中医药杂志》2024年第12期6466-6471,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81673881,No.81202644);河北省自然科学基金项目(No.H2016423049,No.H2022423375);河北省重点研发计划项目(No.223777121D);河北省研究生创新资助项目(No.CXZZBS2021090)。

摘　　要：目的:基于短链脂肪酸受体通路探究中药复方逍遥散调节慢性应激模型大鼠糖代谢的变化机制。方法:SD大鼠随机分为正常组、模型组、氟西汀组和逍遥散组,每组12只,适应性喂养1周,模型组、逍遥散组和氟西汀组大鼠采取慢性温和不可预知应激(CUMS)方法造模,同时每天灌胃相应药物。观察各组大鼠血糖、行为学变化;ELISA检测血清和结肠组织中胰高血糖素样肽1(GLP-1)、酪酪肽(PYY)含量,qRT-PCR检测大鼠结肠组织中G蛋白偶联受体(GPR)41、GPR43、GLP-1、PYY mRNA表达变化,Western Blot检测结肠组织中GPR41、GPR43蛋白表达情况。结果:与正常组比较,模型组大鼠行为学中央区穿格次数、开放臂进入次数显著减少(P<0.01),空腹血糖第2~6周显著升高(P<0.01),糖耐量实验中在0、30、90 min时点显著升高(P<0.01);结肠组织中GLP-1、PYY、GPR41、GPR43 mRNA表达显著减少(P<0.05,P<0.01);血清及结肠组织中GLP-1、PYY含量显著降低(P<0.05,P<0.01);结肠组织中GPR41、GPR43蛋白表达显著降低(P<0.01)。与模型组比较,逍遥散干预后大鼠中央区穿格次数、开放臂进入次数显著增加(P<0.01),空腹血糖在第2、4、5、6周显著降低(P<0.01,P<0.05),糖耐量在30 min时点显著回调,结肠组织GLP-1、PYY、GPR41、GPR43 mRNA表达显著升高(P<0.01,P<0.05),血清和结肠组织中PYY、GLP-1含量显著升高(P<0.01,P<0.05),结肠组织GPR41、GPR43蛋白表达量显著增加(P<0.01,P<0.05)。结论:逍遥散可通过调节结肠组织中GPR41、GPR43、GLP-1、PYY表达变化,进而改善慢性应激引起的抑郁大鼠糖代谢异常。Objective:To investigate the mechanism of glucose metabolism in rats in a chronic stress model based on the short-chain fatty acid receptor pathway by the Chinese herbal compound Xiaoyaosan.Methods:SD rats were randomly divided into normal,model,Fluoxetine and Xiaoyaosan groups,12 rats in each group,and fed for 1 week.The changes in blood glucose and behaviour of rats in each group were observed;ELISA was used to detect the contents of glucagon-like peptide-1(GLP-1)and peptide YY(PYY)in serum and colon tissue,and qRT-PCR was used to detect the expression changes of G protein-coupled receptors(GPR)41,GPR43,GLP-1,and PYY mRNA in rat colon tissue.Western Blot was used to detect the expression of GPR41 and GPR43 proteins in colon tissues.Results:Compared with the normal group,the number of central zone crossing and open entries in the model group rats was significantly reduced(P<0.01),fasting blood glucose increased significantly from 2 to 6 weeks(P<0.01),glucose tolerance test was significantly increased at 0,30 and 90 min(P<0.01).GLP-1,PYY,GPR41,GPR43 mRNA expression decreased(P<0.05,P<0.01),the contents of GLP-1 and PYY in serum and colon tissues were significantly decreased(P<0.05,P<0.01)and the protein expressions of GPR41 and 43 were significantly decreased(P<0.01).After the intervention of Xiaoyaosan,compared with the model group,the times of central region crossing and open-arm entry were significantly increased(P<0.01),fasting blood glucose was significantly decreased at the 2nd,4th,5th and 6th weeks(P<0.01,P<0.05)and glucose tolerance was significantly decreased at 30 min.GLP-1,PYY,GPR41 and GPR43 mRNA expression significantly increased(P<0.01,P<0.05)in colon tissues,the contents of PYY and GLP-1 in colon tissues and serum were significantly increased(P<0.01,P<0.05),and the protein expressions of GPR41 and GPR43 in colon tissues were significantly increased(P<0.01,P<0.05).Conclusion:Xiaoyaosan ameliorates chronic stress-induced abnormalities in glucose metabolism in rats by modulating colonic GPR41,GPR43,GL

关 键 词：逍遥散 慢性不可预知温和应激 糖代谢异常 抑郁 短链脂肪酸受体 

分 类 号：R58[医药卫生—内分泌]