2型糖尿病大鼠海马组织中PGC-1α和SIRT1表达的变化及意义  

Changes of PGC-1α and SIRT1 expression in hippocampus of type 2 diabetes mellitus rats and its significance

作　　者：李斐[1] 赵瑛[1] 

机构地区：[1]第二军医大学长征医院神经内科,上海200003

出　　处：《第二军医大学学报》2013年第4期393-397,共5页Academic Journal of Second Military Medical University

基　　金：国家重点基础研究发展计划("973"计划;2005CB23304)~~

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)和PGC-1α的上游调节蛋白沉默信息调节因子2相关酶类1(SIRT1)在2型糖尿病大鼠海马组织中表达的变化及其意义。方法对SD大鼠进行高脂饲养,用链脲佐菌素一次性腹腔注射诱发SD大鼠糖尿病模型后,将大鼠随机分为模型组和α-硫辛酸组,另设正常对照组。8周后,通过Morris水迷宫实验检测大鼠的认知功能;采用TUNEL法检测海马组织细胞凋亡情况,透射电镜下观察海马组织超微结构;用RT-PCR技术检测海马组织中PGC-1αmRNA的表达,用蛋白质印迹分析方法检测海马组织中PGC-1α及SIRT1蛋白的表达;用试剂盒检测海马组织中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)活性及丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠认知功能下降(P<0.05);海马组织细胞凋亡明显,细胞结构欠清晰,线粒体破坏明显;海马组织中PGC-1αmRNA及蛋白的表达量均降低(P<0.01)),SIRT1蛋白表达量也降低(P<0.01);海马组织中SOD、GSH活性降低(P<0.01),MDA含量升高(P<0.01)。与模型组相比,α-硫辛酸组大鼠认知功能提高(P<0.05);海马组织细胞凋亡及超微结构的破坏均有不同程度的改善;海马组织中PGC-1αmRNA及蛋白的表达量、SIRT1蛋白表达量、SOD活性、GSH活性均升高(P均<0.01),MDA含量降低(P<0.05)。结论高糖环境抑制了SIRT1蛋白的表达,致使PGC-1α的正常生物学功能无法发挥,这可能是糖尿病认知功能损害的一个重要因素。Objective To study the changes in expression of peroxisome proliferator-activated receptor-У co-activator-1α （PGC-1α） and sirtuin （silent mating type information regu1αtion 2 homolog）1 （S. cerevisiae） （SIRT1） in the hippoeampal tissues of type 2 diabetes mellitus rats and to discuss its significance. Methods Diabetic models were induced by high-fat diet and intraperitoneal injection of streptozotocin （STZ） in SD rats. Then the rats were divided into model group and a-lipoic acid group randomly. Healthy rats served as corltrols. All of the rats were tested by Morris water maze after 8 weeks, and then the hippocampus tissues of animals were prepared for TUNEL assay and transmission electron microscopy （TEM） observation, The expression of PGC-1α mRNA was examined by RT-PCR, and the expression of PGC-1 a and SIRT1 protein were examined by Western blotting analysis. Moreover, the activities of superoxide dismutase （SOD）, glutathione （GSH）, and the content of malondialdehyde （MDA） were all examined using corresponding kits. Results Compared with the control group, 8 weeks 1αter the model group had significantly decreased cognitive function （P〈0. 05）, with evident apoptotic neurons and prominent ultrastructure damage in the hippocampus tissues. Moreover, the model group had significantly lower SOD and GSH activities, PGC-1 a mRNA and protein expression, and SIRT1 protein expression （P^0.01）, and significantly higher MDA content （P〈 0.01）. When compared with the model group, rats in the a-lipoic acid group showed significantly improved cognitive function （P〈0.05） and lower levels of neuron apoptosis and ultrastructure damage; and the expressions of PGC-1α mRNA and protein, S1RT1 protein and the activities of SOD and GSH were significantly increased in the a-lipoie acid group （P〈0.01）, while the content of MDA was significantly declined （P〈0.05）. Conclusion High glucose condition inhibits the expression of S1RT1,resulting in the dysfunction of PG

关 键 词：糖尿病神经病变 SIRT1 PGCC-1α 海马 氧化性应激 

分 类 号：R587.25[医药卫生—内分泌]