摘要
目的:进行双益方对2型糖尿病模型大鼠的药效作用实验,分析其作用机制。方法:采用高脂饲养加25 mg·kg^(-1)剂量链脲佐菌素腹腔注射的方法建立2型糖尿病大鼠模型,将成模动物随机分为模型组,二甲双胍组[灌胃(ig),85 mg·kg^(-1)],双益方高、中、低(ig,2 000,1 000,500 mg·kg^(-1))剂量组。进行双益方对2型糖尿病模型大鼠的体重,饮食量,饮水量,二便情况,血糖,糖耐量测定(oral glucose tolerance test,OGTT),糖化血红蛋白(hemoglobin A1c,Hb A1c),糖化血清蛋白(glycosylated serum protein,GSP),胰岛素等指标的检测,蛋白免疫印迹法(Western blot)测定肝组织蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B,PTP1B),蛋白激酶(Akt),磷酸化的蛋白激酶(p-Akt),糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β),磷酸化的糖原合成酶激酶-3β(p-GSK-3β)的表达,Western blot测定骨骼肌组织胰岛素受体底物-1(insulin receptor substrate-1,IRS-1),磷酸化的胰岛素受体底物-1(p-IRS-1),葡萄糖转运蛋白4(glucose transporter 4,Glut4)表达的影响。结果:与模型组比较,双益方可降低2型糖尿病模型大鼠的空腹血糖(fasting blood glucose,FBG),Hb Alc水平及胰岛素抵抗指数(Homa-IR),缓解2型糖尿病模型大鼠饮食量多、饮水量多、二便量大及体重减轻的状况(P<0.05,P<0.01),降低血清胰岛素、糖化血清蛋白、糖化血清蛋白及随机血糖(P<0.05,P<0.01),其中双益方高剂量组药效较好;双益方可显著升高2型糖尿病模型大鼠骨骼肌p-IRS-1,Glut4的表达(P<0.01,P<0.05);双益方可显著升高2型糖尿病模型大鼠肝脏p-Akt的表达,显著降低PTP1B,p-GSK-3β的表达(P<0.01,P<0.05)。结论:双益方可有效调节2型糖尿病模型大鼠糖代谢紊乱,促进胰岛素分泌,改善胰岛素抵抗;调节骨骼肌PI3K/Akt,肝脏Akt/GSK-3β信号转导通路可能是该复方治疗2型糖尿病的作用机制。
Objective： To analyze the pharmacological effect and action mechanism of Shuangyi prescription（ SYP） in the treatment of type 2 diabetes rats. Method： High fat diet plus 25 mg·kg^-1streptozotocin were intraperitoneally injected to establish type 2 diabetic rats model. The model animals were randomly divided into model group,metformin group（ ig,85 mg·kg^-1）,SYP high dose group（ ig,2 000 mg·kg^-1）,SYP middle dose group（ ig,1 000 mg·kg^-1）,and SYP low dose group（ ig,500 mg·kg^-1）. Body weight,food intake,water intake,urine,stool,blood glucose,oral glucose tolerance test（ OGTT）,hemoglobin A1c（ Hb A1c）,glycosylated serum protein（ GSP）,and insulin of type 2 diabetes rats were studied; Western blot was used to detect protein tyrosine phosphatase 1B（ PTP1B）,Akt,p-Akt,glycogen synthase kinase-3β（ GSK-3β）,p-GSK-3β expressions in liver tissues; Western blot to detect insulin receptor substrate-1（ IRS-1）,p-IRS-1,glucose transporter 4（ Glut4） expressions in skeletal muscle tissues. Result： SYP can reduce fasting blood glucose（ FBG）,Hb A1 c level and OGTT of type 2 diabetes rats,reduce insulin resistance index. Compared with the model group,SYP can alleviate polydipsia,polyphagia,polyuria,and weight loss conditions in type 2 diabetic rats in each dose group（ P〈0. 05,P〈0. 01）,SY can reduce insulin,glycated serum protein and random blood glucose（ P〈0. 05,P〈0. 01）,the effect of SYP was better in the high-dose group; SYP can significantly increase p-IRS-1 and GLUT4expressions（ P〈0. 01,P〈0. 05）,reduce the expression of PTP1B（ P〈0. 01,P〈0. 05） in skeletal muscles of type 2 diabetic model rats; SY can significantly increase p-Akt expression,and significantly reduce PTP1 B,pGSK-3β expressions（ P〈0. 01,P〈0. 05） in liver of type 2 diabetic model rats. Conclusion： SYP can effectively regulate glycometabolic disorders in type 2 diabetes rats,improve insulin resistance. The regulation of skeletal muscle PI3K/Akt and liver Akt/GSK-3�
作者
田春雨
薄海美
林飞武
喇孝瑾
曹慧娟
朱亮
杨雨旸
李继安
TIAN Chun-yu BO Hai-mei LIN Fei-wu LA Xiao-jinI CAO Hui-juan ZHU Liang YANG Yu-yang LI Ji-an(College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan 063210, China Clinical Medicine College of North China University of Science and Technology, Tangshan 063210, China Linyitang Pharmaceutical Co. Ltd. , Handan 056004, China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第22期137-142,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河北省自然科学基金项目(H2015209025)
河北省高等学校科学技术研究项目(QN2015119)
