肝部分切除术对老年小鼠认知功能及海马tau蛋白磷酸化的影响

Effect of partial hepatectomy on tau phosphorylation in hippocampus and cognitive function in elderly mice

目的探讨肝部分切除术对老年小鼠认知功能及海马tau蛋白磷酸化的影响。方法将48只C57BL/6老年小鼠随机分为假手术组(n=24)和肝部分切除术组(以下简称手术组,n=24),两组根据手术后测试时间的不同分为术后12 h、1 d、3 d、7 d 4个亚组,各亚组6只。用Morris水迷宫和免疫组化法检测各组小鼠认知功能和海马tau蛋白磷酸化的变化。结果 与术前和假手术组比较,手术组术后3 d和7 d水迷宫测试找到平台的潜伏期明显延长,跨越原平台次数减少(P<0.05);免疫组化染色结果显示手术组磷酸化tau蛋白阳性细胞数高于同时点的假手术组(P<0.01)。结论老年小鼠肝部分切除术后可出现短期认知功能障碍,与海马tau蛋白异常磷酸化有密切关系。

Objective To investigate the effect of partial hepatectomy on the expression of phosphorylated tau in hippocampus and cognitive function in elderly mice. Methods Fourty-eight mice were randomly assigned to two groups （n= 24） ： sham surgery and partial hepatectomy group. Each group was further divided into 4 subgroups, including the subgroups of 12 h, 1 d, 3 d and 7 d after operation, and 6 mice were harvested in each subgroup. Tau phosphorylation and cognitive function were measured by immunocytochemistry and Morris water maze test. Results Compared with the preoperative and the sham group, the latency for mice to find the flat was obviously prolonged and the times to cross the flat were decreased in the partial hepatectomy group 3 d and 7 d post operation （P〈0.05） in the Morris watermaze test. The immunochemistry staining of brain slices showed that the positive cell number of phosphorylated tau markedly increased in the partial hepatectomy group in comparison with that in the sham group （P〈0.01）. Conclusions Partial hepatectomy could induce tau phosphorylation and cognitive deficit within a certain period of time, the level of tau phosphorylation in hippocampus was somehow correlated with the cognitive deficit in mice.