二氮嗪对Alzheimer病模型大鼠行为学及其相关凋亡因子的影响

目的   建立β-淀粉样蛋白1-42（Aβ1-42）致Wistar大鼠阿尔茨海默病(AD)模型，探讨二氮嗪干预后大鼠行为学及其相关凋亡因子表达的变化。方法   大鼠双侧侧脑室注射Aβ1-42两周后诱导建立AD模型，部分大鼠同时注射二氮嗪干预。通过Y型迷宫电刺激评价大鼠学习和记忆能力，采用蛋白电泳方法检测大鼠大脑皮层和海马部位神经细胞内凋亡因子（Bcl-2）、半胱天冬氨酸蛋白酶 3（Caspase-3）表达水平的变化。结果  与正常对照组和生理盐水组比较，Aβ1-42组大鼠学习记忆能力下降，大脑皮层和海马部位神经细胞Bcl-2表达量减少，Caspase-3表达量增加（P<0.01）。与Aβ1-42组比较，二氮嗪+ Aβ1-42组大鼠学习记忆能力有所提高，神经细胞Bcl-2表达量增加，Caspase-3表达量减少（P<0.05）。结论  二氮嗪能提高Aβ1-42组大鼠的学习记忆能力，可能具有抗细胞凋亡的作用。

Effect of diazoxide on the change of apoptotic factors and the ethology of rat Alzheimer disease model

Objective   To establish Alzheimer disease（AD） models of Wistar rats using β-amyloid1-42 (Aβ1-42) and study the effect of diazoxide on the change of apoptotic factors and the ethology of rat AD models. Methods  Aβ1-42 was injected into the bilateral ventricles of all the rats, and two weeks later the AD models were established. Diazoxide were  injected into some rats at the same time. Y maze electric stimulation was used to evalue the capability of study and memory of the rats, and protein electrophoresis was used to detect the expressions of Bcl-2 and Caspase-3 in cortical layer and hippocampus of the rats. Results   The capability of study and memory descended, the expression of Bcl-2 decreased and the expression of Caspase-3 increased in the rats injected with Aβ1-42 compared with the normal rats and thoses injected with NS (P<0.05). The capability of study and memory raised, the expression of Bcl-2 increased and the expression of Caspase-3 decreased in the rats injected with Aβ1-42 and diazoxide compared with the rats injected with Aβ1-42 alone(P<0.05). Conclusions  The AD models were established by the injection of Aβ1-42 into the bilateral ventricles of the rats. Diazoxide can improve the capability of study and memory, increase Bcl-2 expression and decrease Caspase-3 expression. It is likely that diazoxide could resist neurons apoptosis induced by Aβ1-42.