糖尿病导致的脑内氧化应激增加和蛋白质氧化损伤加剧是脑血管病变和阿尔茨海默样病变发生的重要促进因素，蛋白酶体是细胞内参与氧化损伤蛋白质代谢最重要的途径，研究证实蛋白酶体激活因子PA28是能够上调蛋白酶体水解酶活性的内源性蛋白。我们前期的实验发现糖尿病大鼠脑内PA28表达增加和蛋白酶体水解酶活性增加的现象，二者之间的相关性以及对氧化损伤蛋白质代谢是否产生影响有进一步研究的价值。本项目首先建立不同时程的糖尿病大鼠模型，在此基础上系统研究不同时程糖尿病脑内中PA28α、PA28β的表达变化，通过体内外干预改变PA28表达后探讨糖尿病脑PA28α、PA28β表达改变-蛋白酶体活性-氧化损伤蛋白质三者之间的相关性。最后对糖尿病脑内可能导致PA28α、PA28β表达变化的影响因素进行初步探讨。通过本研究，我们希望从代谢调节的角度加深对糖尿病脑内氧化损伤蛋白质加剧机制的了解。

Oxidative stress increase caused by diabetes is great accelerative factor for diabetes associated cerebrovascular diseases and Alzheimer like changes. The proteasome is the most important structure in eukaryotic cells for degrading oxidative damaged proteins. It is well verified by many studies that endogenous the proteasome activator 28 (PA28）proteins can increase proteasome proteolytic activity in cell. Our previous experiments showed increased PA28 proteins and changes in proteasome proteolytic activity. However, the relationship between above experiment phenomenon and the further influence on oxidative damaged protein degradation remains unknown, which have scientific value to study. In this program, we want to invastigate brain PA28α、PA28β changes in eatablished different time period diabetic rats. Further, we design experiments to study the relationship among PA28, proteasome activity and oxidative protein aggregation by PA28α、PA28β intervention studies in vivo and in vitro. Further , we want to investigate the influence factors in diabetes which may induce PA28 changes. Though this study, we hope to deepen understanding about the mechanism underlying oxidative damaged proteins aggregation in diabetic brains from aspect of protein degradation regulation.