[1]孙治坤,马兴荣,陈　帅,等.丁苯酞对糖尿病合并阿尔茨海默病大鼠记忆能力的影响[J].新乡医学院学报,2021,38(2):112-117.[doi:10.7683/xxyxyxb.2021.02.003]
　SUN Zhikun,MA Xingrong,CHEN Shuai,et al.Effect of butylphthalide on the memory ability of rats with diabetes mellitus and Alzheimer′s disease[J].Journal of Xinxiang Medical University,2021,38(2):112-117.[doi:10.7683/xxyxyxb.2021.02.003]
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丁苯酞对糖尿病合并阿尔茨海默病大鼠记忆能力的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
38
期数:
2021年2
页码:
112-117
栏目:
基础研究
出版日期:
2021-02-05

文章信息/Info

Title:
Effect of butylphthalide on the memory ability of rats with diabetes mellitus and Alzheimer′s disease
作者:
孙治坤1; 马兴荣2; 陈　帅1; 贺　爽1; 张杰文1
(1.河南省人民医院神经内科，河南　郑州　4500032.郑州大学第一附属医院神经内科，河南　郑州　450052)
Author(s):
SUN Zhikun1; MA Xingrong2; CHEN Shuai1; HE Shuang1; ZHANG Jiewen1
（1.Department of Neurology,Henan Provincial People′s Hospital,Zhengzhou 450003,Henan Province,China2.Department of Neurology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China）
关键词:
阿尔茨海默病; 糖尿病; 丁苯酞; 氧化应激; 炎症反应
Keywords:
Alzheimer′s diseasediabetes mellitusbutylphthalideoxidative stressinflammatory
分类号:
R332；R749.16
DOI:
10.7683/xxyxyxb.2021.02.003
文献标志码:
A
摘要:
目的　探讨丁苯酞对糖尿病合并阿尔茨海默病大鼠记忆能力的影响。方法　将32只健康Wistar大鼠随机分为空白对照组、模型组、丁苯酞对照组及丁苯酞治疗组，每组8只。模型组和丁苯酞治疗组大鼠腹腔内注射链脲佐菌素（55 mg·kg-1）制备糖尿病模型，然后在大鼠双侧海马组织中注射凝集态的β-淀粉样蛋白制备糖尿病合并阿尔茨海默病模型；空白对照组和丁苯酞对照组大鼠腹腔内注射等体积柠檬酸缓冲液，然后双侧海马组织中注射等体积生理盐水。丁苯酞对照组和丁苯酞治疗组大鼠分别于造模后1周开始灌胃给予丁苯酞（80 mg·kg-1），每日2次，连续给药4周；空白对照组和模型组大鼠每日给予等量的玉米油灌胃。采用Morris水迷宫实验评估各组大鼠学习记忆能力；采用比色法检测各组大鼠大脑皮层和海马组织中乙酰胆碱酯酶（AchE）、胆碱乙酰转移酶（ChAT）、超氧化物歧化酶（SOD）活性及丙二醛（MDA）、谷胱甘肽（GSH）水平；采用酶联免疫吸附试验检测各组大鼠海马组织中白细胞介素（IL）-1β、IL-6水平。结果　丁苯酞对照组与空白对照组大鼠逃避潜伏期、游泳距离、在目标象限中游泳时间百分比和游泳距离百分比、海马组织中IL-1β和IL-6水平及大脑皮层和海马组织中AchE、ChAT、SOD活性、MDA、GSH水平比较差异均无统计学意义（P＞0.05）。训练前3 d，4组大鼠逃避潜伏期及游泳距离比较差异均无统计学意义（P＞0.05）；训练第4天，模型组大鼠逃避潜伏期和游泳距离均长于空白对照组（P＜0.05）；丁苯酞治疗组大鼠逃避潜伏期和游泳距离均短于模型组（P＜0.05）。模型组大鼠在目标象限内游泳时间百分比和游泳距离百分比均显著低于空白对照组（P＜0.05）；丁苯酞治疗组大鼠在目标象限内游泳时间百分比和游泳距离百分比均显著高于模型组（P＜0.05）。与空白对照组比较，模型组大鼠大脑皮层和海马组织中AchE活性及MDA水平显著升高，SOD、ChAT活性及 GSH水平显著降低（P＜0.05）。与模型组比较，丁苯酞治疗组大鼠大脑皮层和海马组织中AchE活性及MDA水平显著降低，SOD、ChAT活性及GSH水平显著升高（P＜0.05）。模型组大鼠海马组织中IL-1β、IL-6水平显著高于空白对照组（P＜0.05）丁苯酞治疗组大鼠海马组织中L-1β、IL-6水平显著低于模型组（P＜0.05）。结论　丁苯酞可显著减轻糖尿病合并阿尔茨海默病大鼠的记忆能力损伤，其作用机制可能与减轻脑内的氧化应激及炎症反应有关。
Abstract:
Objective　To investigate the effect of butylphthalide on memory ability of rats with diabetes mellitus and Alzheimer′s disease.Methods　　Thirty-two healthy Wistar rats were randomly divided into blank control group,model group,butylphthalide control group and butylphthalide treatment group,with 8 rats in each group.The rats in the model group and butylphthalide treatment group were intraperitoneally injected with streptozotocin (55 mg·kg-1) to make the diabetes mellitus model,and then the agglutinated β-amyloid was injected into the bilateral hippocampus of rats to establish the model of diabetes mellitus with Alzheimer′s disease;the rats in the blank control group and butylphthalide control group were intraperitoneally injected with equal volume of citric acid buffer,and then were injected with equal volume of normal saline into the bilateral hippocampus.Rats in the butylphthalide control group and butylphthalide treatment group were given butylphthalide (80 mg·kg-1) by gavage twice a day for 4 weeks after modeling;the rats in the blank control group and model group were given the same amount of corn oil by gavage every day.The learning and memory ability of rats in each group was measured by Morris water maze test;the activities of acetylcholinesterase (AchE),choline acetyltransferase (ChAT),superoxide dismutase (SOD) and the levels of malondialdehyde (MDA),glutathione (GSH) in cerebral cortex and hippocampus of rats in each group were detected by colorimetric method;the levels of interleukin（IL）-1β and IL-6 in hippocampus of rats was detected by enzyme linked immunosorbent assay.Results　There was no significant difference in the escape latency,swimming distance,Percentage of swimming time and swimming distance in target quadrant,levels of IL-1β and IL-6 in hippocampus,activities of AchE,ChAT,SOD in cerebral cortex and hippocampus,levels of MDA,GSH in cerebral cortex and hippocampus of rats between the butylphthalide control group and blank control group (P>0.05).There was no significant difference in escape latency and swimming distance of rats among the four groups in 3 days before training (P>0.05).On the fourth day of training,the escape latency and swimming distance of rats in the model group were longer than those in the blank trol group (P＜0.05);the escape latency and swimming distance of rats in the butylphthalide treatment group were shorter than those in the model group (P＜0.05).The percentage of swimming time and swimming distance in the target quadrant of rats in the model group were significantly lower than those in the blank control group (P＜0.05);the percentage of swimming time and swimming distance in the target quadrant of rats in the butylphthalide treatment group were significantly higher than those in the model group (P＜0.05).Compared with blank control group,the AchE activity and MDA levels in cerebral cortex and hippocampus of rats in the model group were significantly increased,and the SOD,ChAT activity and GSH levels were significantly decreased (P＜0.05).Compared with the model group,the AchE activity and MDA levels in cerebral cortex and hippocampus of rats in butylphthalide treatment group were significantly decreased,and the SOD,ChAT activity and GSH levels were significantly increased (P＜0.05).The levels of IL-1β and IL-6 in hippocampus of rats in the model group were significantly higher than those in the blank control group (P＜0.05).The levels of IL-1β and IL-6 in hippocampus of rats in the butylphthalide treatment group were significantly lower than those in the model group (P<0.05).Conclusion　Butylphthalide can significantly reduce the memory impairment of rats with diabetes mellitus and Alzheimer′s disease,and its mechanism may be related to the reduction of oxidative stress and inflammatory reaction in the brain.

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更新日期/Last Update: 2021-02-05