变叶海棠提取物对糖尿病KK-Ay小鼠糖代谢作用及机制研究  

Effect and Mechanism of Malus toringoides (Rehd.) Hughes. Extract on Glucose Metabolism in Diabetic KK-Ay Mice

作　　者：华桦 刘俐 刘芳[3] 赵军宁[2] 沈岚[1] Hua Hua;Liu Li;Liu Fang;Zhao Junning;Shen Lan(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203;Institute of Translational Pharmacology and Clinical Application,Sichuan Academy of Chinese Medicine Sciences,Sichuan Institute for Translational Chinese Medicine,Biological Assay Key Laboratory of State Administration of Traditional Chinese Medicine for Traditional Chinese Medicine Quality,Engineering Research Center for Formation Principle and Quality Evaluation of Genuine Medicinal Materials in Sichuan Province,Sichuan Engineering Technology Research Center of Genuine Regional Drug,Translational Chinese Medicine Key Laboratory of Sichuan Province,Chengdu 610041;West China School of Pharmacy,Sichuan University,Chengdu 610041)

机构地区：[1]上海中医药大学中药学院,上海201203 [2]四川省中医药科学院转化药理与临床应用研究所,四川省中医药转化医学中心,国家中医药管理局中药质量生物评价重点研究室,四川省道地药材形成原理与品质评价工程研究中心,四川省道地药材系统开发工程技术研究中心,中医药转化医学四川省重点实验室,成都610041 [3]四川大学药学院,成都610041

出　　处：《中药药理与临床》2021年第4期60-64,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金青年科学基金项目(编号:81703820)。

摘　　要：目的:研究变叶海棠提取物对自发性2型糖尿病KK-Ay小鼠糖代谢作用及可能的作用机制。方法:以10只C57/6J小鼠作为正常对照组,50只空腹血糖值大于11.1 mol/L的KK-Ay小鼠随机分为模型对照组、罗格列酮2.67 mg/kg组、变叶海棠0.75、1.50、3.00 g生药/kg组,每组10只,连续灌胃35 d。实验期间每周固定时间测定小鼠体重和空腹血糖值,给药第21 d测定口服葡萄糖耐量;末次给药后摘除眼球取血,收集血清,测定糖化血红蛋白(GHbA1c)和糖基化终末产物(AGEs)水平;检测肾周脂肪组织磷酸化蛋白激酶(p-AKT)和磷酸化糖原合酶激酶-3β(p-GSK-3β)蛋白表达。结果:与正常对照组比较,模型对照组小鼠体质量、空腹血糖值、口服葡萄糖耐量试验中各时间点血糖值及曲线下面积(Auc)、血清GHbA1c和AGEs水平均显著升高,肾周脂肪组织p-AKT和p-GSK 3β蛋白表达显著下调(P<0.01)。与模型对照组比较,变叶海棠提取物各剂量组均能明显降低KK-Ay小鼠体质量和空腹血糖值(P<0.05或P<0.01);口服糖耐量试验中,变叶海棠提取物各剂量组各时间点血糖值及Auc值均明显降低(P<0.05或P<0.01);变叶海棠3.00 g生药/kg组血清GHbA1c和AGEs浓度显著降低(P<0.01)、p-AKT和p-GSK 3β蛋白表达显著上调(P<0.01)。结论:变叶海棠提取物对自发性2型糖尿病KK-Ay小鼠具有明显的降血糖作用,其作用机制可能是通过上调p-AKT和p-GSK 3β表达实现的。Objective:To study the effects of Malus toringoides(Rehd.)Hughes. extract on glucose metabolism in spontaneous type 2 diabetes KK-Ay mice and its possible mechanism. Methods:Ten C57/6 J mice were used as the normal control group. Fifty KK-Ay mice with fasting blood glucose higher than 11.1 mol/L were randomly divided into model control group, rosiglitazone(2.67 mg/kg) group, and M. toringoides extract(0.75,1.50,3.00 g crude drug/kg) groups, with 10 mice in each group, and administrated via gavage for 35 days. During the administration, body weight and fasting blood glucose were measured at a fixed time every week, and oral glucose tolerance was measured on 21 th day of administration. After the last administration, eyeball was removed for blood collection. Serum was collected for the determination of GHbA1 c and AGEs levels. The protein expression of phosphorylated protein kinase(P-AKT) and phosphorylated serine/threonine kinase(P-GSK 3β) were detected in perirenal adipose tissue. Results: Compared with the normal control group, the model control group showed elevated body weight, fasting blood glucose, blood glucose and area under curve(AUC) in oral glucose tolerance test, GHbA1 c and AGEs levels in serum while down-regulated protein expression of p-Akt and P-GSK 3β in perirenal adipose tissue(P<0.01). Compared with the model control group, all the doses of M. toringoides extract significantly reduced the body weight and fasting blood glucose in KK-Ay mice(P<0.01 or P<0.05). In oral glucose tolerance test, the blood glucose and AUC value decreased at each time point in all the M. toringoides extract groups(P<0.01 or P<0.05). The 3.00 g crude drug/kg M. toringoides extract group showed decreased serum levels of GHbA1 c and AGEs(P<0.01) while up-regulated protein expression of P-Akt and P-GSK 3β(P<0.01). Conclusion: The extract of M. toringoides has a significant blood glucose-lowering effect on spontaneous type 2 diabetes KK-Ay mice, which may be related to the up-regulated expression of P-Akt and P-GSK 3β.

关 键 词：变叶海棠 糖尿病 糖代谢 作用机制 

分 类 号：R285.5[医药卫生—中药学]