目的：探讨滋补脾阴方药对糖尿病认知功能障碍大鼠皮质线粒体功能障碍的预防作用机制。方法：SD大鼠随机分为空白对照组（Con），糖尿病组（DM），滋补脾阴方药治疗组（ZBPYR1）和滋补脾阴方药预防组（ZBPYR2）。水迷宫测试大鼠学习记忆能力；透射电镜观察皮质线粒体超微结构、数量变化；Western Blot检测Cyto C表达。结果：①DM组较Con组学习记忆能力下降（P<0.05）；ZBPYR1组学习记忆能力较DM组改善（P<0.05），ZBPYR2组较DM组改善较为明显（P<0.01）。②DM组皮质线粒体数量较Con组减少（P<0.05），线粒体形态发生肿胀、变形、嵴走向紊乱、模糊甚至溶解；ZBPYR干预后上述结果得到改善，且ZBPYR2组较DM组线粒体数量增多（P<0.05）。③DM组胞浆中Cyto C较Con组增强（P<0.01），ZBPYR干预后Cyto C表达减弱。结论：ZBPYR调节皮质区线粒体形态、数量的变化，阻止线粒体中Cyto C向胞浆中释放，提高糖尿病大鼠认知功能。

This study was aimed to observe the protection of Zi-Bu Pi-Yin recipe (ZBPYR) on the cortex mitochondrial dysfunction of diabetes-associated cognitive dysfunction rats. SD rats were randomly divided into four groups, which were the control (Con) group, the diabetes (DM) group, the ZBPYR treatment (ZBPYR1) group and the ZBPYR protection (ZBPYR2) group. Morris water maze test was taken to evaluate the learning and memory ability of rats. The transmission electron microscope (TEM) was used to detect the ultrastructure and quantity changes of cortex mitochondria. Western blot was used to detect the expression of Cyto C. The results showed that compared to Con group, the learning and memory ability were decreased in the DM group (P < 0.05); the learning and memory ability of the ZBPYR1 group was improved compared to the DM group (P < 0.05); compared to the DM group, the ZBPYR2 group was significantly improved (P < 0.01). Compared with the Con group, the number of cortex mitochondria in DM group was decreased (P < 0.05), and the structure was disordered, blurred, or even completely destroyed. After ZBPYR intervention, these pathological changes were reduced obviously. And the number of mitochondria in the ZBPYR2 group was increased than that of the DM group (P < 0.05). The expression of Cyto C in cytoplasm of the DM group was significantly higher than that of the Con group (P < 0.01). After ZBPYR intervention, the expression of Cyto C was decreased. It was concluded that ZBPYR regulated the mitochondrial morphology and changes of volume in the cortex, prevented the releasing of Cyto C from mitochondria to cytoplasm, and improved the cognitive function of diabetes rats.

国家自然科学基金委重点项目（81230084）：情志所致糖尿病认知功能障碍的机理及滋补脾阴法防治基础研究，负责人：战丽彬；教育部高等学校博士学科点专项科研基金（20112105110006）：滋补脾阴法对糖尿病认知功能障碍的作用及其线粒体相关机制，负责人：战丽彬；中国博士后科学基金面上项目（2013M541232）：糖尿病认知功能障碍致线粒体损伤机制及滋补脾阴法干预，负责人：孙铮。