益糖康对db/db小鼠脑内铁调素表达及铁沉积的调节作用  

Regulatory effect of Yitangkang Decoction on the expression of hepcidin and iron overload in the hippocampus of db/db mice

作　　者：安继仁 赵亚硕[2] 张驰[1] 杨宇峰[1] 石岩[1] AN Ji-ren;ZHAO Ya-shuo;ZHANG Chi;YANG Yu-feng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Hebei University of Chinese Medicine,Shijiazhuang 050200,China)

机构地区：[1]辽宁中医药大学,沈阳110847 [2]河北中医学院,石家庄050200

出　　处：《中华中医药杂志》2022年第5期2875-2880,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家中医药领军人才支持计划-岐黄学者(No.[2018]12);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:观察益糖康对db/db小鼠脑铁的调节以及铁调素(hepcidin)的调控作用。方法:将24只db/db小鼠随机分为模型组(db/db组)、利拉鲁肽组(LIRA组)以及益糖康组(YTK组),每组8只。另取8只db/m小鼠作为正常对照组(db/m组)。YTK组予以益糖康煎剂灌胃30 g·kg-1·d-1,LIRA组每日腹腔注射利拉鲁肽200μg·kg-1·d-1,db/m组和db/db组给予等量蒸馏水灌胃。给药5周后,免疫荧光检测海马神经元特异性核蛋白(NeuN)、微管相关蛋白(MAP2)、胶质纤维酸性蛋白(GFAP)及铁调素(hepcidin)表达,免疫组化检测海马hepcidin表达,Western blot检测海马hepcidin、铁蛋白轻链(FTL)、铁蛋白重链(FTH)、转铁蛋白受体(TfR1)、二价金属离子转运体(DMT1)、膜铁转运蛋白(FPN1)蛋白表达,普鲁士蓝染色观察小鼠脑铁分布,qPCR检测海马hepcidin、TfR1、FPN1 mRNA表达。结果:与db/m组比较,db/db组NeuN与MAP2表达显著下降(P<0.01),GFAP表达显著上升(P<0.01),海马铁沉积显著增多(P<0.01),FTH及FPN1表达显著降低(P<0.05,P<0.01),TfR1与DMT1表达显著上升(P<0.01,P<0.05),hepcidin蛋白与mRNA表达均显著升高(P<0.05,P<0.01);与db/db组比较,YTK组小鼠海马NeuN、MAP2表达显著升高(P<0.01,P<0.05),GFAP表达显著降低(P<0.01),海马铁沉积得到显著改善(P<0.01),FTH及FPN1表达显著上调(P<0.05),TfR1与DMT1表达显著下调(P<0.01),hepcidin蛋白与mRNA的过表达均显著抑制(P<0.01)。结论:益糖康可通过调节hepcidin表达并降低糖尿病小鼠脑铁的沉积,缓解神经损伤。Objective:To observe the regulation of Yitangkang Decoction on brain iron in db/db mice and the regulation of hepcidin.Methods:Twenty-four db/db mice were randomly divided into 3 groups:model group(db/db group),liraglutide control group(LIRA group)and Yitangkang Decoction group(YTK group),8 in each one.Eight db/m mice were selected as a control group(db/m group).The YTK group was given Yitangkang decoction 30 g·kg-1·d-1 by gavage,and the LIRA group was given intraperitoneal injection of liraglutide 200μg·kg-1·d-1.The db/m group and db/db group were given the same volume of distilled water by gavage.Five weeks after dosing,the expression of NeuN,MAP2,GFAP and hepcidin in hippocampus were detected by immunofluorescence,hepcidin expression were detected by immunohistochemistry,and hepcidin,FTL,FTH,TfR1,DMT1,FPN1 protein expression in hippocampus were detected by Western blot.Iron distribution in mouse brain were detected by Perls’staining,and qPCR were used to detect the mRNA expression of hepcidin,TfR1,FPN1.Results:Compared with the db/m group,the expression of NeuN and MAP2 in the db/db group decreased(P<0.01),GFAP expression increased(P<0.01),hippocampal iron deposition increased(P<0.01),FTH and FPN1 expression decreased(P<0.05,P<0.01),TfR1 and DMT1 expression increased(P<0.01,P<0.05),and hepcidin protein and mRNA expressions were significantly increased(P<0.05,P<0.01);Compared with the db/db group,the expression of NeuN and MAP2 in the hippocampus of the YTK group were significantly increased(P<0.01,P<0.05),the expression of GFAP was significantly reduced(P<0.01),the iron deposition in the hippocampus was significantly improved(P<0.01),the expression of FTH and FPN1 were upregulated(P<0.05),the expression of TfR1 and DMT1 were down-regulated(P<0.01),and the over-expression of hepcidin protein and mRNA were significantly obtained improve(P<0.01).Conclusion:Yitangkang Decoction could reduce brain iron deposition through the regulation of hepcidin and relieve nerve damage in db/db mice.

关 键 词：糖尿病 认知功能障碍 神经元 益糖康 铁沉积 铁调素 

分 类 号：R285.5[医药卫生—中药学]