新降糖颗粒对2型糖尿病大鼠胰岛素抵抗及肝脏GK表达的影响

Effects of Xinjiangtang Granules on Insulin Resistance and Hepatic GK mRNA Expression in Type 2 Diabetes Mellitus Rats

目的:观察新降糖颗粒对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠血清空腹胰岛素水平(fasting insulin,FINS),超氧化物歧化酶(superoxide dismutase,SOD),丙二醛(malondialdehyde,MDA),C-反应蛋白(C-react protein,CRP)及肝脏葡萄糖激酶(glucokinase,GK)基因的影响,探讨其降糖机制。方法:将SD大鼠随机分为正常对照组和糖尿病造模组。采用高脂饮食联合小剂量ip链脲佐菌素(STZ)28 mg·kg-1建立2型糖尿病模型,造模成功后大鼠随机分为模型组,新降糖颗粒高、中、低剂量组(22.8,11.4,5.7 g·kg-1),二甲双胍组(0.15 g·kg-1)。正常对照组和模型组给予生理盐水,各给药组分别ig给予相应剂量药物。连续ig 5周后,氧化酶法检测大鼠空腹血糖(fasting blood-glucose,FBG)的变化;ELISA法检测大鼠血清中的FINS,CRP的变化;试剂盒检测大鼠血清中SOD,MDA的水平;RT-qPCR法检测肝脏中GK mRNA的表达。结果:与正常对照组比较,模型组中大鼠的FBG,胰岛素抵抗指数(insulin resistance index,IRI)及血清中FINS,CRP含量均显著升高(P<0.01),血清中SOD活性明显降低(P<0.01),新降糖颗粒高、中、低剂量组FBG,IRI,FINS,CRP活性均明显降低(P<0.05,P<0.01),SOD活性明显升高(P<0.05,P<0.01);模型组大鼠肝脏中GK mRNA的表达明显降低(P<0.05),新降糖颗粒中、低剂量组GK mRNA表达量显著升高(P<0.01)。结论:新降糖颗粒能明显降低T2DM大鼠血糖,其可能的作用机制是通过降低糖尿病IRI水平,增强抗氧化应激能力,减轻炎症反应,以及提高肝脏GK mRNA水平而起作用。

Objective：To observe the effects of the Xinjiangtang granule on the serum levels of insulin,superoxide dismutase （SOD）,malondialdehyde （MDA）,C-reactive protein （CRP） and the expression of hepatic glucokinase （GK） mRNA in type 2 diabetes mellitus （T2DM） rats,and to explore its anti-diabetic mechanisms.Method：SD rats were randomly divided into normal group and diabetic group.The model of T2DM rats were established by feeding with high fat diet and injecting low dosage of streptozotocin （STZ） at 28 mg ·kg^-1 Then the rats in diabetic group were randomly divided into model group,metformin group （0.15 mg ·kg^-1）,and low-,medium-,high-dosage groups of Xinjiangtang granule （22.8,11.4,5.7 g ·kg^-1）.The rats in normal and model groups were given the same dosage of normal saline.All rats received oral administration of corresponding medicines for 5 weeks.The levels of fosting blood glucose （FBG） were assayed by oxidase method.The serum levels of fasting insulin （FINS） and CRP were assayed by ELISA.The serum levels of SOD and MDA were detecteded by assay kits.The expression of GK mRNA was detected by RT-qPCR.Result：Compared with the normal group,the levels of FBG,insulin resistance index （IRI）,FINS,CRP showed obvious increase （P 〈0.01）,and serum SOD level showed an obvious decrease in the model group （P 〈 0.01）.The levels of FBG,IRI,MDA,CRP of the high-,medium-and low-dosage Xinjiangtang granule group showed obvious decrease （P 〈 0.01）,the levels of FBG,IRI,FINS,CRP showed obvious decrease （P 〈 0.05,P 〈 0.01） in the low-dosage Xinjiangtang granule group,and serum SOD level showed an obvious increase as compared with those in model group （P 〈0.05,P 〈0.01）.The expression of hepatic GK mRNA showed an obvious decrease in model group as compared with that in normal group （P 〈 0.05）.While it showed an obvious increase in medium-and low-dosage Xinjiangtang granule group as compared with that in model group （P 〈0.01）.Conclusion：The Xinjiangtang granule can significantly reduce the blood glucose level in T2DM rats,which may be achieved by reducing FINS level,enhancing the capacity of resistance to oxidative stress,relieving inflammation and improving the hepatic GK mRNA level.