光甘草定对2型糖尿病的缓解作用及机制  

Mitigative effects of glabridin against type 2 diabetes mellitus and related mechanisms

作　　者：冯亚娟[1] 冯亚静[2] 周建华[1] 王旭东[3] 孙鹏 FENG Yajuan;FENG Yajing;ZHOU Jianhua;WANG Xudong;SUN Peng(Department of Pharmacy,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,Henan Province,China;Department of Infection Management,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China;Department of Pharmacy,the Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450002,Henan Province,China)

机构地区：[1]郑州大学第二附属医院药学部,河南郑州450014 [2]郑州大学第一附属医院感染管理科,河南郑州450052 [3]河南中医药大学第二附属医院药学部,河南郑州450002

出　　处：《新乡医学院学报》2025年第4期266-276,共11页Journal of Xinxiang Medical University

基　　金：河南省高校科技创新团队支持计划(编号:14IRTSTHN017)。

摘　　要：目的探讨光甘草定(GLA)对2型糖尿病(T2DM)的缓解作用及机制。方法将36只清洁级Sprague-Dawley大鼠随机分为对照(CON)组、GLA对照(CON-GLA)组、糖尿病(DM)组、低剂量GLA(GLA-L)组、高剂量GLA(GLA-H)组和二甲双胍(MET)组。CON组和CON-GLA组大鼠给予正常饲料喂养;DM组、GLA-L组、GLA-H组和MET组大鼠给予高糖高脂饲料喂养,连续喂食3周制备T2DM大鼠。然后,CON组大鼠给予正常饲料并腹腔注射0.5 mL二甲基亚砜(DMSO);CON-GLA组大鼠给予正常饲料并腹腔注射0.5 mL GLA(40 mg·kg^(-1));DM组大鼠给予高糖高脂饲料并腹腔注射0.5 mL DMSO;GLA-L组大鼠给予高糖高脂饲料并腹腔注射0.5 mL GLA(20 mg·kg^(-1));GLA-H组大鼠给予高糖高脂饲料并腹腔注射0.5 mL GLA(40 mg·kg^(-1));MET组大鼠给予高糖高脂饲料并腹腔注射MET(150 mg·kg^(-1));每组大鼠均每2日给药1次,持续28 d。分别于给药第0、7、14、21、28天禁食10 h后测量大鼠体质量、空腹血糖(FBG),最后一次给药后1 d行葡萄糖耐量试验(OGTT),并计算时间-血糖曲线下面积(AUC);应用酶联免疫吸附法检测空腹胰岛素(FINS)和糖化血红蛋白(HbA1c)水平,计算胰岛素抵抗指数(HOMA-IR)和胰岛β细胞功能指数(HOMA-β);同时应用酶标仪检测血清中丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平,油红O染色观察大鼠肝脏脂肪沉积情况,并检测各组大鼠肝脏组织中三酰甘油(TG)和总胆固醇(TC)水平;采用Western blot法检测大鼠肝脏糖代谢不同途径中的关键限速酶丙酮酸羧化酶(PC)、葡萄糖-6-磷酸酶(G6Pase)、柠檬酸合酶(CS)和异柠檬酸脱氢酶2(IDH2)蛋白的表达。结果给药第0、7、14、21、28天时,DM组、GAL-L组、GAL-H组、MET组大鼠体质量均显著低于CON组(P<0.05);给药第14、21、28天,GAL-L组、GAL-H组、MET组大鼠体质量显著高于DM组,GAL-H组和MET组大鼠体质量显著高于GAL-L组(P<0.05)。给药第0、7、14、21和28天,DM组、GAL-L组大鼠FBObjective To investigate the mitigative effect of glabridin(GLA)against type 2 diabetes mellitus(T2DM)and its mechanisms.Methods Thirty-six clean Sprague-Dawley(SD)rats were randomly divided into a control(CON)group,a GLA control(CON-GLA)group,a diabetes mellitus(DM)group,a low dose GLA(GLA-L)group,a high dose GLA(GLA-H)group and a metformin group(MET).The rats in CON and CON-GLA groups were given normal feeding.The rats in DM,GLA-L,GLA-H and MET groups were fed with a high-sugar and high-fat diet for 3 weeks to prepare T2DM rats.Then,while being fed with their respective diets,rats in the CON,CON-GLA,DM,GLA-L,GLA-H,and MET groups were given an intraperitoneal injection of 0.5 mL dimethyl sulfoxide(DMSO),0.5 mL GLA(20 mg·kg^(-1)),0.5 mL GLA(40 mg·kg^(-1))and 150 mg·kg^(-1)MET every two days for consecutive 28 days,respectively.The body weight(BW)and fasting blood glucose(FBG)were measured on Days 0,7,14,21 and 28 of administration after fasting for 10 h.Moreover,the oral glucose tolerance test(OGTT)was performed 1 day after the final administration,and the glucose area under the curve(AUC)was calculated.Fasting insulin(FINS)and glycated hemoglobin A1c(HbA1c)levels were measured by enzyme linked immunosorbent assay.Homeostatic model assessment for insulin resistance(HOMA-IR)and homeostatic model assessment forβ-cell function(HOMA-β)were calculated.At the same time,the serum levels of alanine amino-transferase(AST)and aspartate amino-transferase(ALT)were detected by a microplate reader.Fat deposition in the rat liver was observed by oil red O staining,and the liver triglyceride(TG)and total cholesterol(TC)content was detected.The expression of key rate-limiting enzymes pyruvate carboxylase(PC),glucose-6-phosphatase(G6Pase),citrate synthase(CS)and isocitrate dehydrogenase 2(IDH2)in different pathways of liver glucose metabolism was detected by Western blot assay.Results The BW of rats in DM,GLA-L,GLA-H and MET groups was significantly lower than that in the CON group on Days 0,7,14,21 and 28 of administration(P

关 键 词：光甘草定 2型糖尿病 糖代谢 丙酮酸羧化酶 葡萄糖-6-磷酸酶 柠檬酸合酶 异柠檬酸脱氢酶2 

分 类 号：R587.1[医药卫生—内分泌] R966[医药卫生—内科学]