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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 investigate the expression of sIRT1, a regulator of peroxisome proliferator - activated receptor γ - coactivator 1α (PGC - 1α) and PGC - 1α, in hippocampus of type 2 diabetic rats Changes in the expression and its significance. Methods SD rats were fed with high-fat diet and streptozotocin (STZ) -induced diabetic model was induced by intraperitoneal injection of streptozotocin. The rats were randomly divided into model group and α-lipoic acid group, and another normal control group. After 8 weeks, the cognitive function of rats was detected by Morris water maze test; the apoptosis of hippocampus was detected by TUNEL; the ultrastructure of hippocampus was observed by transmission electron microscopy; the expression of PGC-1α mRNA in hippocampus was detected by RT- The protein expressions of PGC-1α and SIRT1 in hippocampus were detected by Western blotting. The activities of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) )content. Results Compared with the normal control group, the cognitive function of the model group was decreased (P <0.05). The apoptosis of hippocampal tissue was obvious, the cell structure was not clear and the mitochondria were damaged obviously. The expression of PGC-1α mRNA and protein in hippocampus (P <0.01). The protein expression of SIRT1 also decreased (P <0.01). The activity of SOD and GSH in hippocampus decreased (P <0.01) and MDA content increased (P <0.01). Compared with model group, α-lipoic acid group increased cognitive function (P <0.05); hippocampal apoptosis and ultrastructure damage in varying degrees improved; hippocampus PGC-1αmRNA and protein SIRT1 protein expression, SOD activity and GSH activity were increased (P <0.01) and MDA content was decreased (P <0.05). Conclusion The high glucose environment inhibits the expression of SIRT1 protein, which leads to the inability of PGC-1α to exert its normal biological function. This may be an important factor in cognitive impairment of diabetes.