短链脂肪酸对术后认知功能障碍老龄大鼠小胶质细胞吞噬突触的影响
Effect of short-chain fatty acids on microglial synapse engulfment in aged rats with postoperative cognitive dysfunction
刘祥 1刘梦琳 2檀晓娜 3于耀宗 2牛俊芳 2王秋筠2
作者信息
- 1. 河北医科大学第三医院麻醉科,石家庄 050051;河北省儿童医院麻醉科,石家庄 050031
- 2. 河北医科大学第三医院麻醉科,石家庄 050051
- 3. 河北省儿童医院神经康复科,石家庄 050031
- 折叠
摘要
目的 评价短链脂肪酸对术后认知功能障碍(POCD)老龄大鼠小胶质细胞吞噬突触的影响.方法 健康雄性SD大鼠48只,18月龄,体质量520～650 g,采用随机数字表法分为4组(n=12):对照组(C组)、短链脂肪酸组(S组)、POCD组(P组)和POCD+短链脂肪酸组(PS组).在S组和PS组大鼠饮水中加入短链脂肪酸(mmol/L,丙酸钠25.9、丁酸钠40、乙酸钠67.5),自由饮水28 d.第29天,P组和PS组大鼠采用4％～5％七氟烷麻醉诱导,3％七氟烷麻醉维持,行胫骨骨折内固定术,制备大鼠POCD模型.于术后7 d时行Morris水迷宫实验,记录逃避潜伏期、穿越原平台位置次数、平均游泳速度和原平台所在象限停留时间.水迷宫实验结束后,麻醉后处死大鼠取完整大脑.高尔基染色分析海马组织CA1区神经元树突棘数量和密度.免疫荧光检测海马组织CA1区突触后致密蛋白95(PSD95)和补体组分蛋白1q(C1q)的表达.结果 与C组比较,P组和PS组大鼠穿越原平台位置次数减少,原平台所在象限停留时间缩短,逃避潜伏期延长,海马CA1区树突棘数量和密度、树突与同心圆交点数减少,PSD95表达下调,C1q表达上调(P＜0.05);与P组比较,PS组大鼠穿越原平台位置次数增多,原平台所在象限停留时间延长,逃避潜伏期缩短,海马CA1区树突棘数量和密度、树突与同心圆交点数增加,PSD95表达上调,C1q表达下调(P＜0.05).结论 短链脂肪酸减轻老龄大鼠POCD的机制与降低小胶质细胞吞噬突触有关.
Abstract
Objective To evaluate the effect of short-chain fatty acids on microglial synapse engulf-ment in aged rats with postoperative cognitive dysfunction(POCD).Methods Forty-eight healthy male Sprague-Dawley rats,aged 18 months,weighing 520-650 g,were divided into 4 groups(n=12 each)using a random number table method:control group(group C),short-chain fatty acids group(group S),POCD group(group P),and POCD+short-chain fatty acids group(group PS).Rats received short-chain fatty acids(sodium propionate 25.9 mmol/L,sodium butyrate 40 mmol/L and sodium acetate 67.5 mmol/L)in the free drinking water for 28 days in S and PS groups.On day 29,anesthesia was induced with 4％-5％sevoflurane and maintained with 3％sevoflurane,and the tibial fracture internal fixation was performed to prepare a rat model of POCD in P group and PS group.Morris water maze test was performed at day 7 after surgery.The escape latency,times of crossing the original platform,mean swimming speed and time spent in the original platform quadrant were recorded.The rats were sacrificed at the end of Morris water maze test,and the brains were collected to analyze the number and density of dendritic spines in the hippocampal CA1 region(by Golgi staining)and to determine the expression of postsynaptic density 95(PSD95)and comple-ment 1q(C1q)in the hippocampal CA1 region(by immunofluorescence).Results Compared with group C,the times of crossing the original platform were significantly decreased,the time spent in the original platform quadrant was shortened,the escape latency was prolonged,the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were decreased,the expression of PSD95 was down-regulated,and the expression of C1q was up-regulated in P and PS groups(P＜0.05).Compared with group P,the times of crossing the original platform were significantly increased,the time spent in the original platform quadrant was prolonged,the escape latency was shortened,the num-ber and density of dendritic spines and the number of intersection points between dendrites and concentric circles were increased,the expression of PSD-95 was up-regulated,and the expression of C1q was down-regulated in group PS(P＜0.05).Conclusions The mechanism by which short-chain fatty acids attenuates POCD is related to decreased microglial engulfment of synapses in aged rats.
关键词
短链脂肪酸/认知功能障碍/老年人/神经元/小胶质细胞/吞噬突触Key words
Short-chain fatty acids/Cognitive dysfunction/Aged/Neuron/Microglia/Engulfment of synapses引用本文复制引用
基金项目
河北省自然科学基金精准医学联合基金重点项目(H2021206021)
出版年
2024
NETL
NSTL
万方数据