锂对慢性铝暴露大鼠脑内CDK5和PP2A表达的影响

Effects of lithium on CDK5 and PP2A expressions in chronic aluminum exposure rats

目的研究锂对慢性铝暴露大鼠脑内周期蛋白依赖性激酶5(CDK5)和蛋白磷酸酯酶2A(PP2A)表达的影响,进一步探讨锂抑制tau蛋白磷酸化的作用机制。方法慢性铝暴露大鼠12只,随机分为锂治疗组和非治疗组。锂治疗组给予氯化锂[200mg/(kg·d)]溶液连续灌胃6周;非治疗组以等量生理盐水灌胃。另取6只同月龄非铝暴露大鼠为正常对照组。Morris水迷宫测试3组大鼠学习记忆功能;Western blotting检测大鼠大脑皮层及海马磷酸化tau蛋白、CDK5、PP2A的表达。结果慢性铝暴露非治疗组大鼠脑内磷酸化tau蛋白含量、CDK5表达明显高于正常对照组大鼠(P<0.05),且慢性铝暴露非治疗组大鼠脑内磷酸化tau蛋白含量与CDK5表达呈正相关(r=0.702,P=0.036)。锂治疗组大鼠脑内磷酸化tau蛋白含量、CDK5表达明显低于非治疗组(P<0.05),且锂治疗组大鼠脑内CDK5表达与磷酸化tau蛋白含量呈正相关(r=0.871,P=0.024),而正常组、锂治疗组和非治疗组大鼠皮层及海马PP2A含量无明显差异(P>0.05)。结论抑制脑内CDK5表达可能是锂降低tau蛋白过度磷酸化,减少大鼠脑内神经原纤维缠结的又一途径。

Objective To explore the effects of lithium on expressions of cyclin-dependent kinase 5 （CDK5） and protein phosphatase 2A （PP2A） in the brains of chronic aluminum exposure rats so as to further understand the mechanism of lithium＇s inhibition on tau phosphorylation. Methods We divided 12 chronic aluminum chloride exposure rats into treatment group and non-treatment group （6 rats in each）. Treatment group was given lithium chloride （200 mg/kg·d） via gastric perfusion daily for 6 weeks,while the non-treatment group sodium chloride at the same dosage and the normal group （6 non-aluminum exposure rats of the same month old） without intervention. Six weeks later,all the rats received Morris water maze test for learning memory function; CDK5 and PP2A expressions and phosphorylated tau protein level in rat hippocampus were determined by Western blotting. Results Compared with normal group,non-treatment of chronic aluminum exposure group showed higher phosphorylated tau protein level and CDK5 expression in the brain （P0.05）,and the level of phosphorylated tau had a significantly positive correlation with CDK5 expression （r=0.702,P=0.036）. After 6 weeks＇ treatment with lithium,phosphorylated tau protein and CDK5 expression decreased significantly in the brain compared with those in non-treatment group （P0.01）. Moreover,phosphorylated tau had a significantly positive correlation with the expression of CDK5 （r=0.871,P=0.024） in lithium treatment group. There was no significant difference in PP2A expression among treatment group,non-treatment group and normal group （P0.05）. Conclusion Lithium may reduce tau phosphorylation and neurofibrillary tangle formation by inhibiting the expression of CDK5.