基于SIRT1/STAT3通路探讨盐酸戊乙奎醚对小鼠学习记忆能力的影响  

Effects of penehyclidine hydrochloride on learning and memory in mice based on SIRT1/STAT3 pathway

作　　者：汪静 张庆国[1] WANG Jing;ZHANG Qing-guo(Department of Anesthesiology,Zhujiang Hospital of Southern Medical University,Guangzhou 510280,Guangdong Province,China)

机构地区：[1]南方医科大学珠江医院麻醉科,广东广州510280

出　　处：《中国临床药理学杂志》2024年第10期1473-1477,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨高剂量盐酸戊乙奎醚(PHC)对小鼠学习记忆能力的影响及其作用机制。方法将60只C57BL/6J小鼠随机分为对照组(腹腔注射等量的0.9%NaCl)、低剂量实验组(腹腔注射0.12 mg·kg^(-1)PHC)、高剂量实验组(腹腔注射5.00 mg·kg^(-1)PHC)、SRT1720组[腹腔注射5.00 mg·kg^(-1)PHC和5 mg·kg^(-1)沉默信息调节因子1(SIRT1)激活药SRT1720],每组15只。给药6 h后,用Morris水迷宫实验和Y迷宫实验检测小鼠学习记忆能力,用蛋白质印迹法检测小鼠海马组织中SIRT1和信号转导及转录激活因子3(STAT3)蛋白的表达水平,用试剂盒检测小鼠海马组织胆碱乙酰转移酶(ChAT)水平,用免疫荧光检测海马组织胶质纤维酸性蛋白(GFAP)阳性表达情况。结果对照组、低剂量实验组、高剂量实验组和SRT1720组小鼠给药6 h后穿越平台次数分别为(6.07±0.44)、(6.00±0.37)、(3.00±0.97)和(4.47±1.31)次,逃避潜伏期分别为(14.02±1.79)、(14.16±1.67)、(51.55±4.07)和(32.84±2.40)s,Y迷宫交替率分别为(60.90±5.18)%、(59.38±5.99)%、(39.80±4.45)%和(46.65±5.02)%,SIRT1蛋白相对表达水平分别为1.05±0.09、1.08±0.12、0.52±0.07和0.77±0.11,STAT3蛋白相对表达水平分别为0.37±0.03、0.38±0.06、0.68±0.06和0.53±0.08,ChAT水平分别为(306.08±20.11)、(296.33±36.11)、(209.99±18.91)和(250.42±25.22)pg·mL-1,GFAP平均光密度值分别为0.05±0.00、0.05±0.00、0.08±0.01和0.06±0.01。高剂量实验组的上述指标与对照组比较,高剂量实验组的上述指标与低剂量实验组比较,SRT1720组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论高剂量的PHC可能通过抑制SIRT1/STAT3通路导致小鼠学习记忆能力下降。Objective To investigate the effects of high-dose pentanethaquine hydrochloride(PHC)on learning and memory in mice and its mechanism.Methods Sixty C57BL/6J mice were divided into control group(intraperitoneal injection of 0.9%NaCl),experimental-L group(intraperitoneal injection of 0.12 mg·kg^(-1)PHC),experimental-H group(intraperitoneal injection of 5.00 mg·kg^(-1)PHC)and SRT1720 group[intraperitoneally injected 5.00 mg·kg^(-1)PHC and 5 mg·kg^(-1)silent information regulator 1(SIRT1)activator SRT1720],15 mice in each group.6 h after administration,learning and memory ability were tested by Morris water maze experiment or Y maze experiment.Western blot assay was used to detect the expression of SIRT1 and signal transducers and activators of transcription-3(STAT3)protein in mouse hippocampus;the levels of choline acetyl transferase(ChAT)in hippocampus of mice were detected by the kit;the expression of glial fibrllary acidic protein(GFAP)in hippocampus was detected by immunofluorescence.Results The times of crossing the platform in control group,experimental-L group,experimental-H group and SRT1720 group were 6.07±0.44,6.00±0.37,3.00±0.97 and 4.47±1.31;the escape latency periods were(14.02±1.79),(14.16±1.67),(51.55±4.07)and(32.84±2.40)s;Y maze alternating rate were(60.90±5.18)%,(59.38±5.99)%,(39.80±4.45)%and(46.65±5.02)%;SIRT1 protein expression levels were 1.05±0.09,1.08±0.12,0.52±0.07 and 0.77±0.11;the expression levels of STAT3 protein were 0.37±0.03,0.38±0.06,0.68±0.06 and 0.53±0.08;ChAT levels were(306.08±20.11),(296.33±36.11),(209.99±18.91)and(250.42±25.22)pg·mL^(-1);the average optical density of GFAP were 0.05±0.00,0.05±0.00,0.08±0.01 and 0.06±0.01.The above indexes of experimental-H group were compared with control group;the above indexes of experimental-H group were compared with experimental-L group;the above indexes of SRT1720 group were compared with experimental-H group;the differences were statistically significant(all P<0.05).Conclusion High dose of PHC may decrease t

关 键 词：盐酸戊乙奎醚 沉默信息调节因子1/信号转导及转录激活因子3信号 学习记忆能力 

分 类 号：R971[医药卫生—药品]