党参多糖对环己酰亚胺所致记忆巩固障碍小鼠脑保护作用的研究  

Research of the brain protective effect of codonopsis pilosula polysaccharide on cycloheximide induced memory consolidation disorder in mice

作　　者：刘梅 安子璇 刘靓靓[1,3] 王风萍 王一頔 李炜 LIU Mei;AN Zi-xuan;LIU Liang-jing;WANG Feng-ping;WANG Yi-di;LI Wei(Department of Pharmacy,Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Drug Dispensing,The Second Affiliated Hospital of Xingtai Medical College,Xingtai 054000,Hebei Province,China;Hebei Key Laboratory of Neuropharmacology,Zhangjiakou 075000,Hebei Province,China)

机构地区：[1]河北北方学院药学系,河北张家口075000 [2]邢台医专第二附属医院药品调剂科,河北邢台054000 [3]河北省神经药理学重点实验室,河北张家口075000

出　　处：《中国临床药理学杂志》2022年第2期127-131,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河北省自然科学基金资助项目(H2020405298);河北北方学院面上基金资助项目(12995363)。

摘　　要：目的研究党参多糖(CPPS)预处理对环己酰亚胺所致记忆巩固障碍小鼠脑保护作用,及其对钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、环腺苷酸反应元件结合蛋白(CREB)蛋白表达的影响。方法将60只昆明种小鼠随机分为空白组、模型组、对照组和低、高剂量实验组,每组12只。按体质量20.0 mL·kg^(-1)的剂量灌胃给药,低、高剂量实验组给予7.5和15.0 mg·mL^(-1)党参多糖,对照组给予25.0 mg·mL^(-1)吡拉西坦,空白组和模型组均给予等体积0.9%NaCl。5组小鼠每天给药1次,连续给药15 d。然后进行Morris水迷宫的空间记忆和空间探索实验,每天继续灌胃给药,并观察各组小鼠的学习记忆巩固能力的变化情况,连续5 d。期间,除空白组,其他各组小鼠按体质量20.0 mL·kg^(-1)的剂量腹腔注射6.0 mg·mL^(-1)的环己酰亚胺抑制记忆蛋白合成,造成小鼠空间记忆巩固障碍。在行为学实验结束后,用蛋白质印迹法检测小鼠海马组织中CaMKⅡ/CREB信号通路相关蛋白的表达情况。结果空白组、模型组、对照组和低、高剂量实验组的平均潜伏期分别为(46.74±10.56),(81.91±17.02),(57.18±15.48),(70.84±17.23)和(61.62±13.77)s,游泳总路程分别为(732.31±181.06),(1 433.36±421.85),(772.45±255.81),(1 060.69±264.03)和(868.21±239.67)cm,第1次穿越平台所在区域潜伏期分别为(31.88±7.39),(50.13±7.99),(36.21±10.65),(30.40±8.53)和(34.29±12.89)s,穿越站台所在区域的次数分别为(2.71±2.22),(0.67±0.44),(1.75±0.84),(1.75±0.65)和(2.04±0.87)次,海马组织中CaMKⅡ/Lamin B1的比值分别为1.61±0.06,0.98±0.08,1.93±0.35,1.19±0.11和1.82±0.19,海马组织中CREB/Lamin B1的比值分别为0.18±0.01,0.06±0.01,0.16±0.02,0.13±0.01和0.17±0.02。对照组及低、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。结论党参多糖可改善由环己酰亚胺所致小鼠的记忆巩固障碍,其机制与上调CaMKⅡ/CREB信号通�Objective To study the brain protective effects of codonopsis pilosula polys accharide(CPPS) on memory consolidation disorder caused by cyclohexylimide, and its effects on the expression of calcium-calmodulin dependent protein kinase Ⅱ(CaMKⅡ) and cAMP-response element binding protein(CREB). Methods Sixty Kunming mice(KM) were randomly divided into blank, model, control, experimental-L and experimental-H groups with 12 mice per group.Mice were given 20. 0 m L·kg^(-1) by intragastric administration. Experimental-L and experimental-H groups were administered with a dose of 7. 5,15. 0 mg·mL^(-1) of CPPS. Control group was administered with a concentration of25. 0 mg·mL^(-1) of piracetam. Blank group and model group were given 0. 9% NaCl at the same volume. All of mice in the 5 groups were given once a day for 15 days. Then,spatial memory and spatial exploration experiments of Morris water maze were carried out. The mice were given by intragastric administration every day,and the changes of learning and memory consolidation ability were observed in each group for 5 days. During this period,except blank group,mice in other groups were intraperitoneally injected with a concentration of 6. 0 mg·mL^(-1) of cycloheximide at a dose of 20. 0 m L·kg^(-1) to inhibit the synthesis of memory protein,causing spatial memory consolidation disorder. After the behavior experiment,the western blot method was used to inspect the protein expression in CaMKⅡ/CREB signaling pathways in the hippocampus of mice. Results The results showed that the escape latencies in the blank,model,control,experimental-L and experimental-H groups were( 46. 74 ± 10. 56),( 81. 91 ± 17. 02),( 57. 18 ± 15. 48),( 70. 84 ±17. 23) and( 61. 62 ± 13. 77) s,the total distance was( 732. 31 ± 181. 06),( 1 433. 36 ± 421. 85),( 772. 45 ±255. 81),( 1 060. 69 ±264. 03) and( 868. 21 ±239. 67) cm,the incubation periods for first crossing the platform area were( 31. 88 ± 7. 39),( 50. 13 ± 7. 99),( 36. 21 ± 10. 65),( 30. 40 ± 8. 53) and( 34. 29 ± 12.

关 键 词：党参多糖 环己酰亚胺 学习记忆 钙调蛋白激酶Ⅱ 环腺苷酸反应元件结合蛋白 

分 类 号：R28[医药卫生—中药学]