二氢杨梅素对2型糖尿病小鼠认知功能障碍的影响

doi:10.12047/j.cjap.5478.2017.079

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (4): 323-328.doi: 10.12047/j.cjap.5478.2017.079

二氢杨梅素对2型糖尿病小鼠认知功能障碍的影响

朱责梅^1,2, 阳际花², 杨丝丝², 何剑琴², 张恺芳², 奉水东³, 凌宏艳²

1. 常德职业技术学院医学系, 湖南常德 415003;
2. 南华大学生理学教研室, 湖南衡阳 421001;
3. 南华大学社会医学与卫生事业管理学教研室, 湖南衡阳 421001

收稿日期:2016-07-25 修回日期:2017-06-16 出版日期:2017-07-28 发布日期:2018-06-19
通讯作者: 凌宏艳,Tel:86-0734-8281389,Tel:86-0734-8281621;E-mail:linghongyan0203@126.com;奉水东,E-mail:shuidong_f@hotmail.com E-mail:linghongyan0203@126.com;shuidong_f@hotmail.com
基金资助:
教育部留学归国基金（教外司留[2014]1685号）；湖南省科技厅（2015JC3085）；湖南省教育厅课题（16C1411）

The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice

ZHU Ze-mei^1,2, YANG Ji-hua², YANG Si-si², HE Jian-qin², ZHANG Kai-fang², FENG Shui-dong³, LING Hong-yan²

1. Department of Medicine, Changde Vocational Technical College, Changde 415003;
2. Department of Physiology, University of South China, University of South China, Hengyang 421001, China;
3. Department of Social Medicine and Health Service Management, University of South China, Hengyang 421001, China

Received:2016-07-25 Revised:2017-06-16 Online:2017-07-28 Published:2018-06-19
Supported by:
教育部留学归国基金（教外司留[2014]1685号）；湖南省科技厅（2015JC3085）；湖南省教育厅课题（16C1411）

摘要/Abstract

摘要： 目的：观察二氢杨梅素（DHM）对2型糖尿病（T2DM）小鼠认知功能障碍及海马中BDNF蛋白表达的影响。方法：将40只C57BL/6J小鼠首先随机分为两组：正常对照组（n=8）：普通饲料喂养；2型糖尿病模型组（n=32）：高糖高脂联合100 mg/kg的STZ处理（造模过程中死亡5只，不成功3只）。24只建模成功的小鼠随机分成3组：T2DM组、T2DM+L-DHM组和T2DM+H-DHM组，3组小鼠高糖高脂喂养，同时分别用等体积生理盐水、125 mg/（kg·d）的DHM和250 mg/（kg·d）的DHM （1次/天，灌胃）处理16周。正常对照小鼠继续普通饲料喂养，同时用等体积生理盐水（1次/天，灌胃）处理16周。16周后测定小鼠体重、空腹血糖、进行腹腔注射葡萄糖耐量实验和相关行为学实验。最后，Western blot检测各组小鼠海马中BDNF蛋白的表达。结果：高糖高脂联合100 mg/kg的STZ成功建立2型糖尿病小鼠模型。16周后，与正常对照组相比，T2DM组小鼠体重明显下降，空腹血糖显著升高，糖耐量显著异常；而T2DM+DHM组相比T2DM组小鼠体重却显著增加、空腹血糖降低，且H-DHM可显著改善T2DM小鼠糖耐量异常。行为学实验结果显示：与正常对照组相比，T2DM组小鼠学习记忆能力明显下降；与T2DM组相比，T2DM+DHM组小鼠学习记忆能力得到改善，且H-DHM组更为明显。Western blot结果显示：与对照组相比，T2DM组小鼠海马中BDNF蛋白表达显著下降，而DHM组相比T2DM组小鼠其BDNF蛋白的表达明显增加。结论：二氢杨梅素可改善2型糖尿病小鼠认知功能障碍，其机制可能通过降血糖作用，并激活海马中BDNF蛋白表达。

关键词: 二氢杨梅素, 2型糖尿病, 小鼠, 认知功能障碍, BDNF

Abstract: Objective: To observe the effects of dihydromyricetin(DHM) on cognitive dysfunction and expression of brain derived neurotrophic factor(BDNF) protein in hippocampus of type 2 diabetic mice(T2DM).Methods: Forty C57BL/6J mice were randomly divided into two groups, normal control group (n=8):normal diet feeding; T2DM model group (n=32):high-glucose and high-fat combined with 100 mg/kg streptozocin(STZ) treatment (five mice died during modeling and three failed). Twenty-four diabetic mice were modeled successfully and divided into three groups (T2DM group, T2DM+L-DHM group and T2DM+H-DHM group). Three groups mice were fed with high-glucose and high-fat diet, and treated with equal volume of normal saline, 125 mg/(kg·d) DHM or 250 mg/(kg·d) DHM for 16 weeks respectively. The control mice were fed with normal diet and treated with equal volume of saline (once a day, gavage) for 16 weeks. After 16 weeks, the body weight and fasting blood glucose were measured, intraperitoneal glucose tolerance test and related behavioral experiment were performed. Finally, the expression of BDNF protein in hippocampus of mice was detected by Western blot.Results: The model of type 2 diabetes mellitus was established successfully with high-glucose and high-fat combined with 100 mg/kg STZ. After 16 weeks, the body weight of T2DM group was significantly decreased, the fasting blood glucose was significantly increased and the glucose tolerance was significantly abnormal compared with the normal control group. Compared with T2DM group, the body weight of T2DM+DHM groups mice was increased, while the levels of fasting blood glucose were decreased. And H-DHM could significantly improve the abnormal glucose tolerance of T2DM mice. Behavior test results showed that the ability of learning and memory of T2DM mice was significant decreased compared with control group, but these phenomena were improved in T2DM+DHM groups mice, and T2DM+H-DHM group was more obvious. Western blot analysis showed that the expression of BDNF protein in hippocampus of T2DM group was significantly lower than that of control group, while T2DM+DHM group was significant increased compared with T2DM mice.Conclusion: Dihydromyricetin can improve the cognitive dysfunction in type 2 diabetic mice. The mechanism may be through hypoglycemic effect and activation of BDNF protein expression in hippocampus.

Key words: dihydromyricetin, type 2 diabetes, mouse, cognitive impairment, BDNF

朱责梅, 阳际花, 杨丝丝, 何剑琴, 张恺芳, 奉水东, 凌宏艳. 二氢杨梅素对2型糖尿病小鼠认知功能障碍的影响[J]. 中国应用生理学杂志, 2017, 33(4): 323-328.

ZHU Ze-mei, YANG Ji-hua, YANG Si-si, HE Jian-qin, ZHANG Kai-fang, FENG Shui-dong, LING Hong-yan. The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice[J]. CJAP, 2017, 33(4): 323-328.

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二氢杨梅素对2型糖尿病小鼠认知功能障碍的影响

The effects of dihydromyricetin on cognitive dysfunction in type 2 diabetes mice

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