白术提取物对db/db小鼠降血糖作用及机制研究  被引量:16

Anti-Diabetic Effect of Extract from Baizhu(白术)on db/db Mice and Its Mechanism

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作  者:张文友 李紫梅 吴礼宜[1] Zhang Wenyou;Li Zimei;Wu Liyi(Sir Run Run Shaw Hospital,Zhejiang University Schol of Medicine,Hangzhou 310000)

机构地区:[1]浙江大学医学院附属邵逸夫医院,杭州310000

出  处:《中药药理与临床》2022年第6期120-125,共6页Pharmacology and Clinics of Chinese Materia Medica

基  金:浙江省自然科学基金(编号:LZ17H280001)。

摘  要:目的:研究白术提物对2型糖尿病db/db小鼠的治疗作用及其与GLP-1R可能的相关机制。方法:50只db/db小鼠随机分为模型对照组、白术提取物50、100、200 mg/kg组、二甲双胍150 mg/kg组,另取10只db/m小鼠作为正常对照组,各组小鼠分别灌胃给予相应的药物,给药第18 d测定口服葡萄糖耐量(OGTT),第21 d检测小鼠血清三酰甘油(TG)、总胆固醇(TC)、空腹血糖(FBG)、空腹胰岛素(FINS)、白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)等指标,计算血糖曲线下面积(AUC)、胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR);HE染色观察肝脏细胞的病理改变情况,油红O染色观察肝细胞脂滴形成情况;Western blotting法检测小鼠肝组织中胰高血糖素样肽-1受体(GLP-1R)、磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、叉头盒蛋白O1(FOXO1)与胰腺和十二指肠同源盒1(PDX-1)的蛋白表达。结果:与正常对照组相比,模型对照组小鼠体质量增长显著增加(P<0.01),血清TG、TC、FBG、FINS、IL-1β和TNF-α含量显著升高(P<0.01),AUC和HOMA-IR显著升高而ISI显著降低(P<0.01),肝脏细胞明显病变,脂滴积聚,肝组织GLP-1R、p-PI3K和PDX-1蛋白表达显著下调,FOXO1的蛋白表达显著上调(P<0.01);与模型对照组相比,白术提取物100、200 mg/kg组小鼠体质量增长明显降低(P<0.05或P<0.01),血清TG、TC、FBG、FINS、IL-1β和TNF-α含量显著降低(P<0.01),AUC和HOMA-IR显著降低(P<0.01),ISI显著升高(P<0.01),小鼠肝脏细胞病变程度明显改善,肝脏脂滴积聚减少,肝脏GLP-1R、p-PI3K和PDX-1蛋白表达显著上调,FOXO1的蛋白表达显著下调(P<0.01)。结论:白术提取物明显调节自发性2型糖尿病小鼠的糖脂代谢紊乱,增强胰岛素敏感性,改善炎症水平,缓解肝脏损伤和脂质沉积,其机制可能与上调肝组织GLP-1R的蛋白表达相关。Objective:To explore the anti-diabetic effect of extract from Baizhu(白术)on type 2 diabetic db/db mice and study the GLP-1 R-related mechanism.Methods:Fifty db/db mice were randomly divided into a model control group,a metformin(150 mg/kg)group,and Baizhu extract(50,100,and 200 mg/kg)groups,and 10 db/m mice were selected as a normal control group.Mice were administrated with corresponding drugs by gavage.The oral glucose tolerance test(OGTT)was detected on the 18^(th) day of administration.The triglyceride(TG),triglyceride(TC),fasting blood glucose(FBG),fasting insulin(FINS),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were determined on the 21^(st) day of administration.The area under the curve of blood glucose(AUC),insulin sensitive index(ISI),and homeostasis model assessment of insulin resistance(HOMA-IR)were calculated.Pathological changes in the liver were observed by hematoxylin-eosin(HE)staining,and lipid droplets were observed by oil red O staining.The protein expression levels of the glucagon-like peptide-1 receptor(GLP-1 R),phosphor-phosphoinositide 3-kinase(p-PI3 K),forkhead box O1(FOXO1),and pancreatic duodenal homeobox-1(PDX-1)were detected by Western blot.Results:Compared with the normal control group,the model control group increased body weight(P<0.01),and increased the content of TG,TC,FBG,FINS,IL-1β,and TNF-α in the serum(P<0.01).It also increased the AUC and HOMA-IR,while decreasing ISI significantly(P<0.01).The hepatocyte steatosis of the model group was significantly aggravated,and lipid droplet accumulation was observed.The protein expression levels of GLP-1 R,p-PI3 K,and PDX-1 were down-regulated(P<0.01),while the protein expression level of FOXO1 was up-regulated in the liver tissue of the model group(P<0.01).Compared with the model group,the groups of extract from Baizhu(100 and 200 mg/kg)decreased the body weight growth of mice(P<0.05 or P<0.01).The levels of TG,TC,FBG,FINS,IL-1βand TNF-α in the serum of mice were decreased(P<0.01),the AUC and HOMA-IR were significa

关 键 词:白术提取物 2型糖尿病 胰高血糖素样肽-1 叉头盒蛋白O1 磷酸化磷脂酰肌醇-3-激酶 

分 类 号:R285.5[医药卫生—中药学]

 

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