摘要
目的研究自发性2型糖尿病OLETF大鼠在疾病发展的不同阶段,其主动脉组织形态学改变以及胰岛素受体底物-1(IRS-1)mRNA的表达水平,探讨胰岛素抵抗状态下大血管病变的发生机制。方法10只OLETF大鼠随机分别在16周龄与24周龄检杀,10只同种系非糖尿病LETO大鼠为正常对照组。应用光镜和透射电镜观察大鼠主动脉组织形态学改变,原位杂交技术检测主动脉IRS-1mRNA表达。结果OLETF大鼠在16周龄时主动脉已出现超微结构异常,至24周时其病变程度加重,表现为典型动脉粥样硬化性早期改变;OLETF大鼠在16周和24周时其主动脉IRS-1 mRNA的表达均明显低于同期LETO对照组,分别减少24.6%(P<0.01)和25.6%(P<0.001)。结论血管组织胰岛素受体后信号传递分子在基因转录水平即存在异常,导致内皮细胞胰岛素抵抗,可能是糖尿病早期大血管病变危险性增加的机制之一。
Objective To study the histopathalogieal changes and the expression of insulin receptor substrate 1 （IRS-1） mNRA in aorta of OLETF rats at different stages and to explore the possible mechanism of maeroangiopathy in insulin- resistant states. Methods OLETF rats（ n = 10） were randomly divided into two groups of 16 weeks and 24 weeks of age. LETO rats（ n = 10） were used as age-matched non-diabetic controls. The histopathologieal changes of thoracic aortas were examined using light-microscope and transmission electron microscope. IRS-lmRNA expression in aorta was estimated by in situ hybridization. Results The aorta in OLETF rats exhibited atheresclerotic lesions from the age of 16 weeks, and progressively developed with aging. Compared with LETO controls, aortic IRS-1 mRNA expression of OLETF rats showed significant decrease of 24.6%（P〈0.01） and 25.6%（P〈0.001）, respectively, at the age of 16 and 24 weeks. Conclusion The reduction of IRS-1 mRNA expression may result in insulin resistance of endothelial cells and also involved in the development of diabetic macroangiopathy.
出处
《中国微循环》
北大核心
2007年第1期27-29,F0003,共4页
Journal of Chinese Microcirculation
