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

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。

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（ T2 DM）. Methods： Forty C57 BL/6 J mice were randomly divided into two groups,normal control group（ n = 8） ： normal diet feeding; T2 DM 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（ T2 DM group,T2 DM＋L-DHM group and T2 DM＋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 T2 DM 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 T2 DM group,the body weight of T2 DM＋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 T2 DM mice. Behavior test results showed that the ability of learning and memory of T2 DM mice was significant decreased compared with control group,but these phenomena were improved in T2 DM＋DHM groups mice,and T2 DM＋H-DHM group was more obvious. Western blot analysis showed that the expression of BDNF protein in hippocampus of T2 DM group was significantly lower than that of control group,while T2 DM＋DHM group was significant increased compared with T2 DM mice. Conclusion： Dihydromyricetin can improve the cognitive dysfunction in type2 diabetic mice. The mechanism may be through hypoglycemic effect and activation of BDNF protein expression in hippocampus.