摘要
目的观察罗格列酮对实验性2型糖尿病大鼠肝脏组织中IRS-2表达的调节,进一步探讨其可能的作用机制。方法采用低剂量链脲佐菌素尾静脉注射联合高脂饲料喂养建立2型糖尿病大鼠模型。未予上述处理的大鼠作为正常对照组(NC组),成模大鼠随机分为糖尿病对照组(UD组)和罗格列酮干预组(RI组)。药物干预4周后,称重,检测血清葡萄糖、胰岛素、甘油三酯和胆固醇,检测大鼠肝脏组织中IRS-2蛋白及mRNA的表达。结果(1)RI组大鼠空腹血糖、胰岛素、甘油三酯水平均低于UD组(P<0.05),高于NC组(P<0.05);RI组血清胆固醇高于NC组(P<0.05),与UD组差异无显著性(P=0.318);(2)免疫印记法示:UD组与NC组相比,肝脏IRS-2蛋白表达明显减少,RI组肝脏IRS-2蛋白表达增加,介于前两者之间,差异均有显著性(P<0.05)。RT-PCR示,UD组较NC组肝脏IRS-2mRNA表达下调,而RI组IRS-2mRNA表达水平介于二者之间。结论IRS-2的继发性减少可能是2型糖尿病的发病机制之一;罗格列酮能够上调IRS-2mRNA及蛋白的表达,这可能是其改善胰岛素抵抗、保护胰岛β细胞的另一作用机制。
Objectives:To investigate the effect of rosiglitazone on insulin receptor substrate2in hepatic tissue of type2diabetic rats,and to explore the different pharmacological mechanism.Methods:The model of type2diabetic rats was established by injecting low dosage of streptozotocin(STZ)and feeding with high fat diet.Then the diabetic rats were divided into two groups:untreated diabetic group(UD)and rosiglitazone-intervened diabetic group(RI).The course of treatment lasted for4weeks.The expression of IRS-2protein was detected by Western blotting.The expression of IRS-2mRNA was detected by RT-PCR.Results:The fasting blood glucose,insulin and triglyceride in RI group were lower than those in UD group,but they were still higher than those of NC group(P<0.05).The result of Western blotting showed that the expression of IRS-2protein in RI group was increased,compared with UD group.But its level was still lower than that in NC group;RT-PCR indicated that the expression of IRS-2mRNA in RI group was increased compared with UD group,although it was still decreased compared with that in NC group.Conclusions:The results of the test indicate that the secondary decrease of IRS-2may play an important role in pathogenesis of type2dia-betes mellitus,and that the mechanism of anti-diabetic action of rosiglitazone may be partly due to improving the expression of IRS-2.
出处
《中国现代医学杂志》
CAS
CSCD
2004年第14期9-13,共5页
China Journal of Modern Medicine
关键词
罗格列酮
2型糖尿病
胰岛素抵抗
胰岛Β细胞
胰岛素受体底物2
rosiglitazone
type2diabetes mellitus
pancreaticβ-cell
insulin resistance
insulin receptor substrate2
