PARP抑制剂对糖尿病大鼠皮层神经元的保护作用  

Protective Effect of PARP Inhibitor on Cortical Neurons in Streptozotocin-induced Diabetic Rats

作　　者：吴晓黎[1] 王智敏[1] 梁鹤缤 郝颖[1] 郑东明[1] 郭阳[1] 

机构地区：[1]中国医科大学附属盛京医院神经内科,沈阳110021

出　　处：《中国医科大学学报》2015年第6期481-484,共4页Journal of China Medical University

基　　金：国家自然科学基金(81000467)

摘　　要：目的研究PARP抑制剂3-氨基苯甲酰(3-AB)对链脲佐菌素诱导的糖尿病(DM)大鼠皮层神经元的作用及机制。方法将60只大鼠随机分假手术对照组、DM组和DM+3-AB组,每组20只。采用Morris水迷宫实验检测大鼠学习记忆能力,采用紫外分光光度计法测定皮层组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量,采用Western blot法检测皮层PARP1蛋白表达水平,采用免疫组化法检测皮层caspase-3表达变化。结果 DM组大鼠学习记忆能力明显下降。DM组的SOD和GSH-Px含量显著低于对照组(P<0.01),MDA含量显著高于对照组(P<0.01),DM+3-AB组的SOD和GSH-Px含量明显高于DM组(P<0.05),MDA含量明显低于DM组(P<0.05)。DM组的PARP1表达显著增加(P<0.01),DM+3-AB组的PARP1表达显著降低(P<0.01)。DM组的caspase-3表达显著高于对照组(P<0.01),DM+3-AB组的caspase-3表达显著降低(P<0.01)。结论 3-AB通过抑制PARP1,减轻DM导致的氧化应激,减少皮层神经元凋亡。Objective To investigate the effect of PARP inhibitor 3-aminobenzamide （3-AB） on cortical neurons in streptozotocin-induced diabetes mellitus （DM） rats and the mechanism. Methods A total of 60 rots were divided into 3 groups randomly： sham-operated control group, DM group and DM＋3-AB group, 20 rats in each group. Morris maze was used to detect learning and memory abilities in each group. Spectrophotometer assay was used to detect the levels of superoxide dismutase （ SOD ）, glutathione peroxidase （GSH-Px） and malondialdehyde （ MDA ） in cortex. Westem blot was used to determine the expression of poly （ADP-ribose） polymerase 1 （PARP1） in cortex. Immunohistochemical staining was used to determine the expression of caspase - 3-immunoreactive neurons in cortex. Results DM rats showed significantly declined learning and memory abilities. Compared with the control group, the levels of SOD and GSH-Px were significantly reduced （P 〈 0.01 ） and the level of MDA was significantly up-regulated （P 〈 0.01 ） in the DM group. Compared with the DM group, the levels of SOD and GSH-Px were significantly higher（P 〈 0.05 ） and the level of MDA was significantly lower in the DM＋3-AB group （P 〈 0.05 ）. The expression level of PARP1 was significantly up-regulated in the DM group and was significantly decreased in the DM＋3-AB group（P 〈 0.01 ）. The level of caspase-3 was significantly higher in the DM group than in the control group （P 〈 0.01 ）, and was significantly decreased in the DM＋3-AB group （P 〈 0.01 ）. Conclusion 3-AB protected cortical neurons from apoptosis in DM rats by inhibition of PARP1 and alleviation of oxidative stress.

关 键 词：糖尿病 PARP 认知障碍 氧化应激 

分 类 号：R743.32[医药卫生—神经病学与精神病学]