Wnt非经典途径对小鼠阿尔茨海默病模型的作用及机制的初步探讨

Preliminary study of non classical pathway and mechanism of Wnt on mice model of Alzheimer's disease effect

目的探讨Wnt非经典途径对小鼠阿尔茨海默病模型的作用以及机制。方法选取90只4个月龄的SD雄性小鼠,随机均分为正常对照组、假手术组、模型组、低剂量组、中剂量组和高剂量组,每组15只。正常对照组不予处理,假手术组注入一定量的生理盐水,模型组、低剂量组、中剂量组和高剂量组的小鼠用基底核注射海人藻酸建立阿尔茨海默病模型,造模成功后连续给药氯化锂,经过小鼠跳台实验测定被动回避次数;处死小鼠后,测定脑组织中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)的浓度变化。结果模型组、低剂量组的被动回避次数与假手术组比较明显升高(P<0.05),高、中剂量组小鼠与模型组比较被动回避次数均明显降低(P<0.05);与模型组比较,低、中和高剂量组细胞因子IL-1β、IL-6、TNF-α明显下降(P<0.05),且中、高剂量组下降更显著(P<0.05)。结论高、中剂量组剂量的氯化锂能显著改善小鼠的学习记忆成绩,且疗效均优于低剂量氯化锂。氯化锂Wnt非经典途径对小鼠阿尔茨海默病模型起积极的作用,有助于改善阿尔茨海默病。

Objective To investigate the role of non classical Wnt pathway on mice model of Alzheimer＇s disease and the mechanism. Methods 90 SD male mice 4 months of age, were randomly divided into normal control group, sham operation group, model group, low dose group, middle dose group and high dose group, 15 mice in each group. The control group was given treatment. The physiological saline was injec- ted into the sham operation group, model group, low dose group, middle dose group and high dose group of mice to establish the cell model of Alzheimerg disease with basal nuclei injection of kainic acid. After the success of modeling continuous administration of lithium chloride, step - down test small rat was measured by passive avoidance the number of times. After sacrifice of mice, the concentration changes in brain tissue by IL - 1, IL - 6, TNF alpha were measured. Results In the model group, the passive avoidance times of low dose group of was significantly increased compared with the sham operation group （ P 〈 0.05 ）. The passive avoidance of high dose group, medium dose group mice decreased significantly compared with the model group （ P 〈0.01 ）. The cytokine IL- 1 beta and IL-6 and TNF alpha in the low dose group, middle dose group and high dose group significantly decreased （ P 〈 0.01 ）. Conclusion High dose group and medium dose group could significantly improve the learn- ing and memory performance, and the efficacy was better than low dose group, the non classical pathway of lithium chloride Wnt to the Alzheimer disease mice model. It can improve the patients with Alzheimer＇s disease.