双益方改善2型糖尿病模型大鼠胰岛素抵抗的药效及作用机制

发布时间：2018-04-07 17:51

本文选题：双益方　切入点：型糖尿病　出处：《中国实验方剂学杂志》2017年22期

【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(P0.05,P0.01),降低血清胰岛素、糖化血清蛋白、糖化血清蛋白及随机血糖(P0.05,P0.01),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(P0.01,P0.05);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(P0.01,P0.05)。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。
[Abstract]:Aim: to study the effect of Shuangyi recipe on type 2 diabetic rats.The indexes of body weight, diet, drinking water, defecation, blood glucose and glucose tolerance in type 2 diabetic rats were measured by Shuangyi recipe, including glucose tolerance test OGTT, hemhemoglobin A1cHbA1C, glycosylated serum protein, insulin and so on.The expression of insulin receptor substrate-1, phosphorylated insulin receptor substrate-IRS-1, glucose-transporter 4(glucose transporter 4 and glucose-transporter 4(glucose transporter 4 in the iliac muscle were observed.Results: compared with the model group, Shuangyi decoction decreased fasting blood glucose and fasting blood glucose level and insulin resistance index (insulin resistance index) in type 2 diabetic rats, and relieved type 2 diabetes rats with more diet and more water consumption.(2) the situation of large feces volume and weight loss, reducing serum insulin, glycosylated serum protein, glycosylated serum protein and random blood glucose (P0.05) P0.01A, among which Shuangyi prescription high dose group had better effect;Shuangyifang significantly increased the expression of p-IRS-1Glut4 in skeletal muscle of type 2 diabetic rats and significantly increased the expression of p-Akt in liver of type 2 diabetic rats, and significantly decreased the expression of p-GSK-3 尾 in the liver of type 2 diabetic rats.Conclusion: Shuangyifang can effectively regulate glucose metabolism disorder, promote insulin secretion and improve insulin resistance in type 2 diabetic rats, and regulate PI3K / Akt, Akt/GSK-3 尾 signal transduction pathway in liver, which may be the mechanism of this compound in the treatment of type 2 diabetes.
【作者单位】：华北理工大学中医学院;华北理工大学临床医学院;河北林益堂药业有限公司;
【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)
【分类号】：R285.5;R-332

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