EGCG改善APP/PS1转基因小鼠认知功能及减轻海马胰岛素抵抗的机制研究

The mechanism study of EGCG on improvement of cognitive function and alleviation of hippocampal insulin resistance in APP/PS 1 transgenetic mice

目的探讨EGCG没食子酸酯(epigaliocatechin—3—gallate,EGCG)减轻APP/PSl转基因小鼠海马胰岛素抵抗并改善认知功能机制。方法 24只12月龄雌性APP/PSl小鼠随机均分为模型组(Tg)、EGCG低剂量组(Tg/EGCG—L)、高剂量组(Tg/EGCG—H),同月龄雌性C 57 BL/6 J小鼠作为对照组(NT)。采用Morris水迷宫检测各组小鼠学习、记忆能力,Western blot和免疫组织化学方法检测各组小鼠海马TNF—α/JNK信号及IRS—1 pSer 312的表达。结果与NT组比较,Tg组小鼠寻找平台的逃避潜伏期及平均路程显著延长(P<0.05),海马TNF—α/JNK信号异常活化、IRS—1 pSer312表达明显升高(P<0.05).EGCG各治疗组较Tg组各异常指标均显著改善(P<0.05)。结论 EGCG可减轻APP/PS1转基因小鼠海马胰岛素抵抗,改善认知功能,其机制可能与其降低TNF—α/JNK信号通路的活化相关。

Objective To explore mechanism of epigallocatechin-3-gallate (EGCG) on improvement of cognitive function and alleviation of hippocampal insulin resistance in APP/PS 1 transgenetic mice. Method 12 months old female APP/PS 1 mice were randomly divided into 3 groups:model group(Tg), EGCG low dose group (Tg/EGCG-L), high dose group(Tg/EGCG-H). C 57 BL/6 J mice were utilized as control. learning and memory ability in 4 group mice were detected by morris water maze test(MWM). The hippocampal TNF-α/JNK signal and IRS-1 pSer 312 expression were detected by Western blot and immunohistochemical staining. Results Compared with NT mice, Tg mice showed a marked prolongation of the escape latency and swimming distance in the MWM test(P<0.05);Abnormal activation of TNF-α/JNK signaling and increased IRS-1 pSer 312 expression in the hippocampus of Tg mice(P<0.05). EGCG-treated Tg mice showed significantly improvement of all these abnormal changes(P<0.05). Conclusion EGCG treatment is able to alleviate hippocampal insulin resistance and improve cognitive function in the APP/PS 1 mice. which may be partly attributed to the reduction of TNF-α/JNK signaling activity in this AD mouse model.