2型糖尿病及阿尔茨海默病大鼠糖原合成酶-3β和tau蛋白磷酸化的研究

Research on glycogen synthase kinase-3β and hyperphosphorylation of tau protein in rats combined type 2 diabetes and Alzheimer＇s disease

目的研究2型糖尿病（T2DM）并发阿尔茨海默病（AD）的可能机制。方法选取同龄Wistar大鼠，随机分为正常对照组、T2DM组、AD组及T2DM＋AD组。采用血糖仪监测大鼠血糖，水迷宫实验观测大鼠行为学改变，免疫组化染色检测大鼠糖原合成激酶-3β（GSK-3β）及tau蛋白磷酸化水平。结果各模型组大鼠均较正常对照组学习记忆力减退，T2DM组与AD组及T2DM＋AD组之间差异有统计学意义（F=28．65P〈0．001）。T2DM＋AD组GSK38表达水平（4319．02±653．24）显著高于T2DM组（540．43±558．49）、正常对照组（315．56±91.64）及AD组（304．39±175．83）（H-19．335，P〈0．001）。AD组（2799．61±1070．02）及T2DM＋AD组（8583．81±2236．11）tau蛋白磷酸化表达水平显著高于正常对照组（252．02±58．37）及T2DM组（287．75±192．53）（H=32．950，P〈0．001）。结论T2DM大鼠GSK-3β活性的上调可能是引起大鼠tau蛋白磷酸化的-个重要原因。

Objective To investigate the possible pathogenesis of type 2 diabetes mellitus （T2DM） combined with Alzheimer＇s disease （AD）. Methods Wistar rats were randomly divided into control, T2DM, AD and T2DM＋AD groups. The blood glucose levels were assayed, and the behavior changes were tested by Morris water maze. The glycogen synthase kinase-3β （GSK-3β） and hyperphosphorylation of tau protein were detected by immunohistochemistry staining. Results Compared with the control rats, the learning and memory abilities were weakened significantly in the model rats （F= 28.65, P〈0. 001）. The expression of GSK 3β was higher in T2DM＋ AD group （4319.02±653.24） than in AD group （304.39±175.83）, T2DM group （540.43±558.49） and control group （315.56±91.64, H=19. 335, all P〈0.01）. The level of hyperphosphorylation of tau protein was significantly increased in T2DM -- AD group （8583.81± 2236.11 ） and AD group （2799. 61±1070. 02） than in control group （252.02±＋-58.37） and T2DM group （287.75± 192.53,H=32. 950, P 〈 0. 001）. There was no significantly difference of hyperphosphorylation of tau between T2DM group and control group （H=32. 950, P〈0.05）. Conclusions The increasing of GSK-3β activity in T2DM may be caused by hyperphosphorylation of tau.