DHM抑制海马内质网应激改善T2DM大鼠认知功能障碍  

DHM improves cognitive dysfunction in T2DM rats by inhibiting hippocampal endoplasmic reticulum stress

作　　者：李梦伟 吕慧婕 王紫涵 罗金定 丁星星 何剑琴 杨丝丝 奉水东[4] 凌宏艳 LI Meng-wei;LYU Hui-jie;WANG Zi-han;LUO Jin-ding;DING Xing-xing;HE Jian-qin;YANG Si-si;FENG Shui-dong;LING Hong-yan(Dept of Physiology,Hengyang Medical College,University of South China,Hengyang,Hunan 421001,China;Physical Education Institute,Jishou University,Xiangxi Hunan 416000,China;Chuanshan College University of Sowth China;Dept of Social Medicine and Health Management,Public Health College,University of South China,Hengyang,Hunan 421001,China)

机构地区：[1]南华大学衡阳医学院生理学教研室,湖南衡阳421001 [2]吉首大学体育科学学院,湖南湘西416000 [3]南华大学船山学院 [4]南华大学公共卫生学院社会医学与卫生事业管理学教研室,湖南衡阳421001

出　　处：《中国药理学通报》2022年第1期91-97,共7页Chinese Pharmacological Bulletin

基　　金：湖南省自然科学基金资助项目(No 2018JJ2347);湖南省自然科学基金资助项目(2021JJ30595);湖南省研究生科研创新项目(No CX20190754);南华大学大学生创新创业项目(No S202012650006)。

摘　　要：目的探讨二氢杨梅素(dihydromyricetin, DHM)对2型糖尿病(T2DM)大鼠认知功能障碍的影响及机制。方法 SD大鼠随机分为正常对照组(n=56):普通饲料+柠檬酸盐缓冲液(30 mg·kg^(-1));T2DM模型组(n=60):高糖高脂+低剂量STZ(30 mg·kg^(-1))(未成功的4只剔除)。将上述2组大鼠分别用或不用DHM处理(250 mg·kg^(-1)·d^(-1),灌胃),12周后,每组随机选取8只大鼠进行Morris水迷宫和Y迷宫检测,观察DHM对大鼠认知功能的影响。各组剩余大鼠分别侧脑室置管给与内质网应激(ERS)拮抗剂牛磺熊去氧胆酸(TUDCA)10μg·d^(-1)或ERS激活剂衣霉素(TUN)10μL,行为学检测之后,取大鼠海马组织,Western blot检测海马ERS蛋白GRP78、p-PERK的表达。结果 DHM和TUDCA均能改善T2DM大鼠认知功能障碍;相反,TUN降低DHM对T2DM大鼠认知功能障碍的改善作用。Western blot显示,TUDCA降低T2DM大鼠GRP78和p-PERK蛋白表达,TUN增加DHM处理的T2DM大鼠GRP78和p-PERK蛋白表达。结论 DHM改善T2DM大鼠认知功能障碍,其机制可能与抑制ERS有关。Aim To investigate the effect of dihydromyricetin(DHM) on cognitive dysfunction in type 2 diabetes mellitus(T2 DM) rats and its mechanism. Methods SD rats were randomly divided into the normal control group(n=56): normal diet and citrate buffer solution(30 mg·kg^(-1));T2 DM model group(n=60): high glucose, fat and low dose STZ(30 mg·kg^(-1))(Four unsuccessful rats were eliminated). Then rats in the above two groups were treated with or without DHM(250 mg·kg^(-1)·d^(-1), intragastric). After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats. The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid(TUDCA) 10 μg·d^(-1)or ERS activator tunicamycin(TUN) 10 μL, respectively. After the behavioral analysis, the hippocampal tissues of rats were taken out. The expressions of ER stress related proteins GRP78 and P-PERK were detected by Western blot. Results Both DHM and TUDCA could improve cognitive dysfunction in T2 DM rats. On the contrary, TUN reduced the effect of DHM on cognitive dysfunction in T2 DM rats. TUDCA decreased the expression of GRP78 and p-PERK proteins in T2 DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2 DM rats treated by DHM. Conclusion DHM improves cognitive dysfunction in T2 DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

关 键 词：二氢杨梅素 2型糖尿病大鼠 认知功能障碍 内质网应激 GRP78 p-PERK 

分 类 号：R-332[医药卫生] R284.1