盐酸硫胺对2型糖尿病大鼠糖脂代谢及肾脏氧化应激的影响及机制的初步研究  

Effect and mechanism of thiamine hydrochloride on glucose and lipid metabolism and renal oxidative stress in experimental type 2 diabetic rats

作　　者：张洁[1] 贾新菊[1] 董闪闪[1] 周慧敏[1] 康岩[1] ZHANG Jie;JIA Xin-ju;DONG Shan-shan;ZHOU Hui-min;KANG Yan(Department of Endocrinology,First Hospital,Hebei Medical University,Hebei Shijiazhuang 050031,China)

机构地区：[1]河北医科大学第一医院内分泌科,河北石家庄050031

出　　处：《中国医院药学杂志》2021年第23期2428-2432,共5页Chinese Journal of Hospital Pharmacy

基　　金：河北省2017年度医学科学研究计划项目(编号:20170501)。

摘　　要：目的:研究盐酸硫胺(THC)对实验性2型糖尿病(T2DM)大鼠糖脂代谢及肾脏氧化应激的影响,并探讨相关机制。方法:30只T2DM大鼠随机分为T2DM组、THC组、THC+磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)抑制剂(LY294002)组,每组各10只,10只健康大鼠设为对照组。THC组灌胃THC 3 mg·kg^(-1),THC+LY294002组灌胃THC 3 mg·kg^(-1),尾静脉注射LY2940020.5 mg·kg^(-1),对照组、T2DM组分别灌胃、尾静脉注射等体积0.9%氯化钠溶液。每天1次,连续8周。检测大鼠糖脂代谢指标、肾组织氧化应激指标、肾组织AKT、p-AKT、叉头状转录因子O1(FoxO1)、p-FoxO1蛋白表达量。结果:与对照组比较,T2DM组FBG、FINS、HOMA-IR、TG、TC、LDL-C含量升高,HDL-C含量降低,给予THC后上述糖脂代谢指标均改善,在THC的基础上给予LY294002可降低THC对糖脂代谢指标的改善作用。与对照组比较,T2DM组肾组织MDA、ROS含量升高,给予THC后上述氧化应激指标均改善,在THC的基础上给予LY294002可降低THC对氧化应激指标的改善作用。与对照组比较,T2DM组肾组织p-AKT/AKT降低、p-FoxO1/FoxO1升高,给予THC后肾组织p-AKT/AKT升高、p-FoxO1/FoxO1降低,在THC的基础上给予LY294002可逆转THC对p-AKT/AKT、p-FoxO1/FoxO1的影响。结论:THC可改善T2DM大鼠糖脂代谢,减轻肾脏氧化应激,可能通过激活PI3K/AKT信号通路来发挥作用。OBJECTIVE To explore the effects of thiamine hydrochloride(THC)on glucose and lipid metabolism and renal oxidative stress in experimental type 2 diabetes(T2DM)rats and elucidate the related mechanisms.METHODS Thirty T2DM rats were randomly divided into three groups of T2DM,THC,THC+LY294002[inhibitor of phosphatei-dylinositol 3 kinase(PI3K)/protein kinase B(AKT)](n=10 each)and 10 healthy rats were designated as control group.THC group was gavaged with THC 3 mg·kg^(-1).THC+LY294002 group was gavaged with THC 3 mg·kg^(-1) and injected with LY2940020.5 mg·kg^(-1) in tail vein.Control and T2DM groups were gavaged and injected with an equal volume of normal saline once daily for 8 weeks.The parameters of glucose and lipid metabolism,kidney tissue oxidative stress,AKT,p-AKT,forkhead transcription factor O1(FoxO1)and p-FoxO1 protein expression in renal tissue were detected.RESULTS As compared with control group,the contents of FBG,FINS,HOMA-IR,TG,TC and LDL-C spiked in T2DM group while HDL-C declined.After THC dosing,the above-mentioned parameters of glucose and lipid metabolism improved.LY294002 could reverse the improvement of THC on glucose and lipid metabolism parameters.As compared with control group,the contents of MDA and ROS in kidney tissue rose in T2DM group.After THC dosing,the above oxidative stress parameters improved.On the basis of THC,LY294002 could reverse the improvement of THC on oxidative stress parameters.As compared with control group,renal tissue p-AKT/AKT decreased and p-FoxO1/FoxO1 rose in T2DM group.After THC dosing,p-AKT/AKT rose and p-FoxO1/FoxO1 dipped.LY294002 could reverse the improvement of THC on p-AKT/AKT and p-FoxO1/FoxO1.CONCLUSION THC can improve glucose and lipid metabolism in T2DM rats and reduce oxidative stress in kidneys.It may play a role by activating the PI3K/AKT signaling pathway.

关 键 词：盐酸硫胺 2型糖尿病 糖脂代谢 肾脏 氧化应激 

分 类 号：R587.1[医药卫生—内分泌]