Effect of Hei Xiaoyaosan on Expression of CaMKⅡα Protein and Its Phosphorylation in Hippocampus and Cerebral Cortex of APP/PS1 Double Transgenic Mice / 中国实验方剂学杂志

ABSTRACT

Objective:To study the effect of Hei Xiaoyaosan on the expression of calcium calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and its phosphorylation in hippocampus and cortex of mice with Alzheimer's disease. Method:After weighing, 30 APP/PSI transgenic male mice were divided into model group, donepezil hydrochloride group and Hei Xiaoyaosan group according to random principle and 10 in each group.At the same age, wild-type C57BL/6 10 mice of the same species were treated as blank group. Donepezil hydrochloride group (6 g·kg-1) and Hei Xiaoyaosan group (3.25 mg·kg-1) were administered for 90 days, then the behavior of all the mice were detected by Morris water maze, the expression of CaMKⅡα, p-CaMKⅡα proteins in hippocampus and cortex by immunohistochemical technique and Western blot. Result:After intervention 3 months, compared with blank group, the average escaping latency periods prolonged significantly and the number of cross-platform and effective areas were decreased distinctly in model group mice(P<0.01), CaMKⅡα protein relative expression decreased significantly(P<0.01), p-CaMKⅡα protein relative expression increased significantly(P<0.01). Compared with the model group, the escape latency of donepezil hydrochloride and Hei Xiaoyaosan group were significantly shortened, and the number of crossing platforms and effective areas was significantly increased (P<0.05, P<0.01), the expression of CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly increased (P<0.01), p-CaMKⅡα protein in the hippocampus and cortex of drug groups was significantly decreased (P<0.05, P<0.01). Conclusion:Hei Xiaoyaosan can improve the learning and memory ability of AD mice by regulating the expression of CaMKⅡα and its phosphorylation, which are key proteins involved in the mechanism of cell memory formation in different brain regions of AD mice.