黄芪黄酮与葛根黄酮配伍对胰岛素分泌的影响

Effects of Astragalus Flavonoids and Kudzu Flavonoids on Insulin Secretion

目的:明确黄芪黄酮与葛根黄酮配伍对胰岛素分泌的调节机制。方法:将SPF级SD雄性大鼠按随机血糖分为6组,即正常组、模型组、金芪降糖片1. 47 g/kg组、黄芪黄酮0. 039 g/kg组(A1B0)、葛根黄酮0. 036 g/kg组(A0B1)、黄芪黄酮+葛根黄酮0. 075 g/kg组(A1B1),每组11只。除正常组外,按照46 mg/kg剂量ip链脲佐菌素(STZ),制备实验性糖尿病大鼠模型,并按照2×2析因设计实验方案实施。分别于给药前、给药第7天、第30天,血糖仪检测血糖水平。给药第30天,酶联免疫法(ELISA)检测胰腺胰岛素(INS)水平;实时荧光定量PCR法(QPCR)检测胰腺过氧化物酶增殖激活受体α(PPARα)、p38丝裂原活化蛋白激酶(p38MAPK)、胰岛素受体底物2(IRS2)、磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B-2(Akt2) mRNA表达。结果:与正常组相比,模型组大鼠INS分泌减少,血糖水平显著升高,PPARα、IRS2、PI3K、Akt2 mRNA表达降低,p38MAPK mRNA表达升高;与模型组相比,黄芪黄酮能显著降低模型大鼠血糖,与葛根黄酮配伍对血糖未见显著影响,配伍间不存在交互作用。黄芪黄酮与葛根黄酮配伍能显著促进INS分泌,调控胰腺PPARα、p38MAPK、IRS2、PI3K、Akt2 mRNA表达,且配伍间存在交互作用。结论:黄芪黄酮与葛根黄酮配伍能改善胰腺INS分泌,其机制可能与协同缓解胰腺脂毒性及炎症反应、调控IRS/PI3K/Akt信号通路有关。

Objective： To explore the regulation mechanism of astragalus flavonoids and kudzu flavonoids on insulin secretion. Method： SPF male SD rats were randomly divided into six groups according to blood glucose,normal group,model group（A0 B0）,jin-qi-jiang-tang tablet group（1. 47 g/kg）,astragalus flavonoids group（A1 B0,0. 039 g/kg）,kudzu flavonoids group（A0 B1,0. 036 g/kg）,astragalus flavonoids and kudzu flavonoids group（A1 B1,0. 075 g/kg）,11 rats in each group. In addition to the normal group,the other groups were induced by streptozocin（STZ,46 mg/kg） to build experimental diabetic rat model. According to the 2 × 2 factorial design,the experiment scheme was implemented. The level of blood glucose was detected by glucose meter on 7 d,30 d respectively. The serum cholesterol（CHO） and triglyceride（TG） levels were detected by biochemical analyzer on 30 d. Enzyme-linked immunosorbent assay（ELISA） was used to test the level of insulin（INS） in pancreas. The gene expression of peroxisome proliferator-activated receptor α（PPARα）,p38 mitogen-activated protein kinase（p38 MAPK）,insulin receptor substrate 2（IRS2）,phosphatidylinositol-3-kinase（PI3 K） and protein kinase B-2（Akt2） in pancreas were assayed by Quantitative Real-Time PCR（QPCR）. Result： Compared with normal group,insulin secretion decreased,the level of blood glucose and lipid（CHO and TG） increased,the mRNA expression of PPARα,IRS2,PI3 K and Akt2 decreased（P 〈 0. 05）,and p38 MAPK mRNA expression increased in model group（P 〈 0. 05）. Compared with model group,astragalus flavonoids reduced blood glucose in rats significantly（P 〈 0. 05）,the compatibility with Kudzu flavonoids has no significant effect on blood glucose,and there was no interaction between the two drugs. The compatibility of astragalus flavonoids and Kudzu flavonoids can significantly promote the secretion of INS,reduced the level of blood lipids,and regulated the mRNA expression of PPARα,p38 MAPK,IRS2,PI3 K,Akt2 in pancreas. There was an interaction effect between the compatibility on above indexes. Conclusion： The compatibility of astragalus flavonoids and Kudzu flavonoids can improve the secretion of INS. The mechanism may be related to synergistic effect of alleviate toxicity,inhibit inflammation response and regulate IRS/PI3 K/Akt pathway in the pancreas.