目的 探究菊苣酸調(diào)節(jié)沉默信息調(diào)節(jié)因子1（Sirt1）/叉頭框蛋白O1（FoxO1）通路對糖尿病腦病大鼠認(rèn)知功能的影響。方法 構(gòu)建糖尿病腦病大鼠模型后，將其隨機(jī)分為模型組、菊苣酸（10、20、40 mg/kg）組、菊苣酸＋EX527組，每組12只，另取12只大鼠作為對照組。Morris水迷宮實驗檢測大鼠空間記憶能力；曠場實驗檢測大鼠運動探索能力；血糖儀檢測空腹血糖（FBG）水平；采用ELISA試劑盒檢測空腹胰島素（FINS）、炎癥指標(biāo)和氧化應(yīng)激指標(biāo)[超氧化物歧化酶（SOD）、丙二醛（MDA）]水平；試劑盒檢測活性氧（ROS）水平；計算胰島素抵抗指數(shù)（HOMA-IR）；采用蘇木素–伊紅（HE）染色觀察海馬組織病理變化，Western blotting檢測凋亡及Sirt1/FoxO1通路相關(guān)蛋白表達(dá)水平。結(jié)果 菊苣酸（10、20、40 mg/kg）組海馬組織結(jié)構(gòu)呈現(xiàn)出逐漸恢復(fù)的趨勢，神經(jīng)細(xì)胞形態(tài)的破壞程度得到改善；菊苣酸＋EX527組海馬組織結(jié)構(gòu)破壞程度有所增加。相較于模型組，菊苣酸（10、20、40 mg/kg）組逃避潛伏期、FBG、FINS、HOMA-IR、腫瘤壞死因子（TNF-α）、白細(xì)胞介素（IL）-1β、IL-6、ROS、MDA水平，半胱氨酸蛋白酶-3（Caspase-3）表達(dá)，Ac-FoxO1/FoxO1值降低；穿越平臺次數(shù)、平均速度、行走總路程、穿越中心區(qū)次數(shù)、SOD水平、Sirt1蛋白表達(dá)升高（P＜0.05）；相較于菊苣酸40 mg/kg組，菊苣酸＋EX527組逃避潛伏期、FBG、FINS、HOMA-IR、TNF-α、IL-1β、IL-6、ROS、MDA水平、Caspase-3表達(dá)、Ac-FoxO1/FoxO1值升高，穿越平臺次數(shù)、平均速度、行走總路程、穿越中心區(qū)次數(shù)、SOD水平、Sirt1蛋白表達(dá)降低（P＜0.05）。結(jié)論 菊苣酸可能通過調(diào)節(jié)Sirt1/FoxO1信號通路改善糖尿病腦病大鼠認(rèn)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

青海省科技廳應(yīng)用基礎(chǔ)研究項目（2021-ZJ-771）