Effects of rosuvastatin calcium combined with donepezil on inflammatory response in mice with Alzheimer’s disease

Abstract:

Objective：To study the effects of rosuvastatin calcium combined with donepezil on the expression of inflammatory factors in rats with Alzheimer’s disease. Methods：APP/PS1 double transgenic mice were randomly divided into model group，donepezil group，rosuvastatin group and combined treatment group，10 mice in each group. The dose of donepezil hydrochloride group[donepezil 1.3 mg/（kg·d） infusion]，rosuvastatin calcium group [rosuvastatin calcium 1 mg/（kg·d） infusion]，combined treatment group[rosuvas－tatin calcium 1 mg/（kg·d），donepezil 1.3 mg/（kg·d） infusion]. The model group was not treated. Morris water maze was used to test the escape latency of mice in each group. Methylene blue staining was used to observe the morphological changes of hippocampal neurons in each group. Immunohistochemical method was used to detect the expression of IL-1β，TNF-α and p38MAPK in hip－pocampus of mice. Western blot was used to detect the content of IL-1β，TNF-α and p38MAPK in hippocampus of mice. Results：After treatment，the escape latency was shortened in donepezil group，rosuvastatin group and combined therapy group，but the combined therapy group was better than donepezil group and rosuvastatin group. The results of immunohistochemistry showed that the average optical density of IL-1β（0.37±0.05 vs. 0.52±0.09，P=0.001），TNF-α（0.42±0.08 vs. 0.69±0.11，P=0.002） and p38MAPK（0.39±0.06 vs. 0.61±0.10，P=0.001） in combined treatment group were lower than that in model group. The results of Western blot showed that the expression of IL-1β，TNF-α and p38MAPK in donepezil group，rosuvastatin group and combined treatment group were lower than that in model group. Conclusion：Rosuvastatin calcium combined with donepezil can significantly im－prove the spatial learning，memory and neuron damage of APP/PS1 transgenic mice. It may decrease the production of inflammatory factors in hippocampus by inhibiting p38MAPK pathway.