目的：观察脾阴虚糖尿病大鼠海马及大脑皮质中不同形式的β淀粉样蛋白（Aβ）、胰岛素降解酶（IDE）变化，及其在脾阴虚糖尿病认知功能障碍中的作用，并观察滋补脾阴法对其影响。方法：将大鼠随机分为空白对照组（Cont）、糖尿病组（DM）、脾阴虚组（pi）、脾阴虚糖尿病组（piDM）、滋补脾阴方药治疗组（ZBPYR）5 组。采用梯度离心的方法提取可溶性与不可溶Aβ，通过ELISA 方法测定各组大鼠海马及大脑皮质中可溶性与不可溶的Aβ1-42 及Aβ1-40 的含量变化，通过Western blot 方法观察各组大鼠海马及皮质中IDE 蛋白表达变化。结果：DM 组、piDM 组大鼠海马、大脑皮质可溶性与不可溶Aβ1-42 均高于Cont 组（P<0.05），ZBPYR 组较DM 组、piDM 组降低了海马、大脑皮质可溶性与不可溶Aβ1-42 的表达（P<0.05）。DM 组、pi 组、piDM 组大脑皮质可溶性Aβ1-40 较Cont 组增加（P<0.05），ZBPYR 组较DM 组、piDM 组有所下降（P<0.05）。DM 组、piDM 组海马IDE 蛋白表达较Cont 组降低（P<0.05），ZBPYR 组海马较DM 组、piDM 组升高（P<0.05）；DM 组、pi 组、piDM 组大鼠大脑皮质IDE 蛋白水平较Cont 组降低（P<0.05），ZBPYR 组大脑皮质较DM 组降低（P<0.05）。结论：脑组织中Aβ1-42 增加可能是糖尿病大鼠、脾阴虚糖尿病大鼠认知功能障碍的主要病理变化，IDE 表达下降可能是导致Aβ1-42 增加的原因之一，滋补脾阴法可能通过上调IDE 蛋白表达降低Aβ1-42 的含量。

This study was aimed to observe different forms of β-amyloid peptide (Aβ) and insulin degrading enzyme(IDE) in the hippocampus and cortex in order to further explore the role of Aβ and IDE on spleen yin deficiency diabetes-associated cognitive decline (DACD), and the effect of Zi-Bu Pi-Yin method. The rats were randomly divided into five groups, which were the blank control (Cont) group, diabetes (DM) group, spleen yin deficiency (pi) group,spleen yin deficiency diabetes (piDM) group and Zi-Bu Pi-Yin recipe (ZBPYR) group. Soluble and insoluble Aβ in the hippocampus and cortex of rats were extracted by gradient centrifugation, and then measured by ELISA. The expression of IDE was observed by western blot. The results showed that the content of soluble and insoluble Aβ1-42 in the hippocampus and cortex of the DM group and piDM group were higher than the Cont group. The soluble and insoluble Aβ1-42 content in the hippocampus and cortex of the ZBPYR group were reduced compared with the DM group and the piDM group. The soluble Aβ1-40 in the cortex of the DM group, pi group and piDM group were increased compared with the Cont group (P < 0.05). The soluble Aβ1-40 content of the ZBPYR group was decreased compared with the DM group and the piDM group (P < 0.05). The expression of IDE protein was decreased in the hippocampus of the DM group and the piDM group compared with the Cont group (P < 0.05), and the IDE protein level in the hippocampus of the ZBPYR group was increased compared with the DM group and the piDM group (P <0.05). The expression of IDE protein in the cortex of the DM group, pi group and piDM group was lower than the Cont group (P < 0.05). The IDE protein level in the cortex of the ZBPYR group was reduced compared to the DM group (P < 0.05). It was concluded that the increased Aβ1-42 in brain may be a major pathological change of DACD and spleen yin deficiency DACD. The decreased IDE expression may be one of the reasons to induce increasing of Aβ1-42 level. The Zi-Bu Pi-Yin method may decrease the Aβ1-42 content by upregulating IDE protein expression.

国家自然科学基金委面上项目（30772847）：糖尿病脑病的内质网应激机制及滋补脾阴方药干预研究，负责人：战丽彬；教育部高等学校博士学科点专项科研基金（20070161004）：脾阴虚痴呆与糖尿病脑病的内质网应激机制研究，负责人：战丽彬；辽宁省教育厅高校优秀人才支持计划（LR2001015）：滋补脾阴方药对糖尿病脑病内质网应激机制的研究，负责人：战丽彬；辽宁特聘教授资助计划，负责人：战丽彬。