金匮肾气丸对糖尿病大鼠骨骼肌胰岛素受体表达的影响

Effects of Jinkui Shenqi Wan on Expression of Insulin Receptor of Skeletal Muscle in Rats with Diabetes

摘要:

目的: 探讨金匮肾气丸(Jinkui Shenqi Wan,JKSQ)对糖尿病大鼠骨骼肌胰岛素受体(insulin receptor, InsR)基因表达的影响,阐明其降低血糖的分子机制.方法: 6周龄的SPF级雄性SD 大鼠高脂高糖饲料喂养4周后,腹腔注射链脲佐菌素制备糖尿病模型.4 d后模型大鼠随机分成模型组、二甲双胍组、JKSQ低、高剂量组.正常组与模型组给予生理盐水,二甲双胍组给予二甲双胍(100 mg ·kg^-1),JKSQ低、高剂量组分别给予JKSQ(10,20 g ·kg^-1)灌胃4周.以酶学方法检测各组大鼠骨骼肌的己糖激酶(hexokinase,HK),6-磷酸果糖激酶-1(6-phosphofructokinase-1,PFK)活性,逆转录实时荧光定量PCR及蛋白印迹法检测骨骼肌InsR mRNA及蛋白表达水平变化.结果: 与正常组比较,模型组出现了HK,PFK活性下降(P<0.01),InsR mRNA及蛋白质表达下降(P<0.01);给药治疗4周后,与模型组相比较,二甲双胍组、JKSQ低、高剂量组HK,PFK活性明显上升(P<0.05);同时各组InsR mRNA及蛋白质表达量明显提高(P<0.05).结论: JKSQ能上调2型糖尿病大鼠骨骼肌InsR 基因在mRNA及蛋白质的表达,增加HK与PFK活性,促进葡萄糖的氧化利用.

Abstract:

Objective:To investigate the effect of Jinkui Shenqi Wan(JKSQ) on insulin receptor (InsR) gene expression in skeletal muscle. Method: With 4 weeks fed high fat high sugar diet, male SD SPF rats of 6 weeks were induced diabete by intraperitoneal injection with streptozotocin. After 4 days the model rats were randomly divided into model group, metformin group, JKSQ low dose group and high dose group. The normal group and model group were given physiological saline, metformin group was given metformin (100 mg · kg^-1), JKSQ low dose group and high dose group were given JKSQ (10, 20 g · kg^-1) by gavage for 4 weeks. Hexokinase (HK), 6-phosphofructokinase-1(PFK) activity of skeletal muscle were detected. The mRNA and protein expression lever of InsR were detected with RT-PCR and Western blot. Result: As compared with normal group, HK and PFK activity decreased in model group (P<0.01), the mRNA and protein expression of InsR were decreased markedly (P<0.01). During 4 weeks with drug treatment, as compared with the model group, medicine HK and PFK activity were significantly increased in positive control group, JKSQ low dose group and high dose group (P<0.05);while each of the above groups InsR expression on mRNA and protein were significantly increased (P<0.05). Conclusion: JKSQ can increase the mRNA and protein lever expression of InsR, and increas HK and PFK activity, to promote the oxidation of glucose utilization in skeletal muscle.