γ-亚麻酸对糖尿病小鼠记忆衰退的影响及机制  

Effect of γ-Linolenic Acid on Memory Decline in Diabetic mice and Its Mechanism

作　　者：石剑[1] 贡丽雅 王燕[1] SHI Jian;GONG Liya;WANG Yan(Department of Nutrition,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院营养科,石家庄050000

出　　处：《转化医学杂志》2024年第2期153-157,共5页Translational Medicine Journal

基　　金：河北省医学科学研究课题计划(20200953)。

摘　　要：目的 探究γ-亚麻酸(GLA)对糖尿病小鼠记忆衰退的影响及机制。方法 选取16只8周龄野生型小鼠,雌雄各半,分成GLA组及对照组,对所有小鼠使用1 g/kg D-果糖加10%饮用水饮食(持续40 d)诱导糖尿病小鼠记忆衰退模型。对照组小鼠给予每日1 mg/kg生理盐水灌胃,GLA组小鼠给予每日1 mg/kg GLA灌胃。干预7 d后,以Morris水迷宫评估小鼠的学习和记忆障碍情况,处死小鼠取大脑皮层及海马组织,以HE染色检查二者病理改变,以透射电镜观察小鼠海马神经元超微结构变化,以Western Blot实验检测小鼠海马组织中GRP78、GRP94、NOX2和NOX4蛋白表达水平。结果 GLA组小鼠的逃逸潜伏期短于对照组,穿越环次数高于对照组(P<0.05)。GLA组小鼠大脑皮层和海马组织病理变化以及海马神经元超微结构损伤程度均较对照组轻。GLA组小鼠海马组织GRP78、GRP94、NOX2和NOX4蛋白表达水平低于对照组(P<0.05)。结论 GLA能通过抑制海马神经元内质网应激反应,进而改善糖尿病小鼠记忆衰退。Objective To explore the effect ofγ-linolenic acid(GLA)on memory decline in diabetic mice and its mechanism.Methods Sixteen 8-week-old wild-type mice,including 8 males and 8 females,were divided into GLA group and control group.All mice were given a diet of 1 g/kg D-fructose plus 10%drinking water(for 40 days)to induce memory decline model of diabetic mouse.Mice in the control group were given 1 mg/kg normal saline by gavage daily,and mice in the GLA group were given 1 mg/kg GLA by gavage daily.After 7 days of intervention,the learning and memory disorders of the mice were assessed by Morris water maze.The cerebral cortex and hippocampus tissues of the mice were collected after the mice were sacrificed,and the pathological changes of the two tissues were examined by HE staining.The ultrastructural changes of neurons in the hippocampus were observed by transmission electron microscopy.The expression levels of GRP78,GRP94,NOX2 and NOX4 proteins in mouse hippocampus were detected by Western blot assay.Results The escape latency of GLA group was lower than that of control group,while the number of loop crossing was higher than that of control group(P<0.05).The pathological changes of cerebral cortex and hippocampal tissue and the damage degree of hippocampal neuron ultrastructure in GLA group were less than those in control group.The expression levels of GRP78,GRP94,NOX2 and NOX4 proteins in the hippocampus of GLA group were lower than those of control group(P<0.05).Conclusion GLA can ameliorate memory decline in diabetic mice by inhibiting endoplasmic reticulum stress response of hippocampal neurons.

关 键 词：Γ-亚麻酸 记忆衰退 糖尿病 内质网应激 海马 GRP78 NOX2 小鼠 

分 类 号：R587.2[医药卫生—内分泌] R-332[医药卫生—内科学]