目的 探究菊苣酸调节沉默信息调节因子1（Sirt1）/叉头框蛋白O1（FoxO1）通路对糖尿病脑病大鼠认知功能的影响。方法 构建糖尿病脑病大鼠模型后，将其随机分为模型组、菊苣酸（10、20、40 mg/kg）组、菊苣酸＋EX527组，每组12只，另取12只大鼠作为对照组。Morris水迷宫实验检测大鼠空间记忆能力；旷场实验检测大鼠运动探索能力；血糖仪检测空腹血糖（FBG）水平；采用ELISA试剂盒检测空腹胰岛素（FINS）、炎症指标和氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）]水平；试剂盒检测活性氧（ROS）水平；计算胰岛素抵抗指数（HOMA-IR）；采用苏木素–伊红（HE）染色观察海马组织病理变化，Western blotting检测凋亡及Sirt1/FoxO1通路相关蛋白表达水平。结果 菊苣酸（10、20、40 mg/kg）组海马组织结构呈现出逐渐恢复的趋势，神经细胞形态的破坏程度得到改善；菊苣酸＋EX527组海马组织结构破坏程度有所增加。相较于模型组，菊苣酸（10、20、40 mg/kg）组逃避潜伏期、FBG、FINS、HOMA-IR、肿瘤坏死因子（TNF-α）、白细胞介素（IL）-1β、IL-6、ROS、MDA水平，半胱氨酸蛋白酶-3（Caspase-3）表达，Ac-FoxO1/FoxO1值降低；穿越平台次数、平均速度、行走总路程、穿越中心区次数、SOD水平、Sirt1蛋白表达升高（P＜0.05）；相较于菊苣酸40 mg/kg组，菊苣酸＋EX527组逃避潜伏期、FBG、FINS、HOMA-IR、TNF-α、IL-1β、IL-6、ROS、MDA水平、Caspase-3表达、Ac-FoxO1/FoxO1值升高，穿越平台次数、平均速度、行走总路程、穿越中心区次数、SOD水平、Sirt1蛋白表达降低（P＜0.05）。结论 菊苣酸可能通过调节Sirt1/FoxO1信号通路改善糖尿病脑病大鼠认知功能。

Objective To explore the effect of cichoric acid on cognitive function in diabetic encephalopathy rats by adjusting Sirt1/ FoxO1 pathway. Methods A diabetic encephalopathy rat model was constructed and randomly grouped, divided into model group, cichoric acid (10, 20, 40 mg/kg) group, and cichoric acid + EX527 group, each had 12 rats: Another 12 rats were taken as the control group. Morris water maze experiment was performed to test the spatial memory ability of rats. The open field experiment was performed to test the motor exploration ability of rats. The blood glucose meter was used to detect FBG. ELISA kits were used to detect the FINS, inflammatory markers, and oxidative stress markers (SOD, MDA). ROS reactive oxygen species detection kit was used to detect ROS. HOMA-IR was calculated. HE staining and Western blotting was used to observe the pathological changes of hippocampal tissues and detect apoptosis and proteins related to the Sirt1/FoxO1 pathway. Results The hippocampal tissue structure of the control group was intact, with tightly arranged and orderly nerve cells and round nuclei. The hippocampal tissue structure of the model group was severely damaged, with disordered arrangement of nerve cells and abnormal morphology. The hippocampal tissue structure in the cichoric acid (10, 20, 40 mg/kg) groups showed a gradually recovering trend, and the degree of damage to the morphology of nerve cells was improved. The degree of hippocampal tissue structure damage in the cichoric acid + EX527 group increased. Compared with the model group, cichoric acid (10, 20, 40 mg/kg) group showed decreases in escape latency, FBG, FINS, HOMA-IR, TNF-α, IL-1β, IL-6, ROS, MDA, Caspase-3, and Ac-FoxO1/FoxO1 ratio, and the number of platform crossings, increases in average speed, total walking distance, number of crossings through the central area, SOD, and Sirt1 protein (P < 0.05). Compared with cichoric acid 40 mg/kg group, cichoric acid + EX527 group showed increases in escape latency, FBG, FINS, HOMA-IR, TNF-α, IL-1β, IL-6, ROS, MDA, Caspase-3, and Ac-FoxO1/FoxO1 ratio, and the number of platform crossings, decreases in average speed, total walking distance, number of crossings through the central area, SOD, and Sirt1 protein (P < 0.05). Conclusion Cichoric acid may improve cognitive function in diabetic encephalopathy rats by adjusting Sirt1/FoxO1 signaling pathway.

R285.5

青海省科技厅应用基础研究项目（2021-ZJ-771）