DHA对糖尿病认知障碍大鼠海马神经元SDF-1/CXCR4通路的影响  

Effects of DHA on diabetes-associated cognitive deficits and SDF-1/CXCR4 signaling pathway in diabetic rats

作　　者：张德平 宋彦泽 谢祥军[1] 王颖[1] 戚瑞[1] 杨瑞华[1] Zhang Deping;Song Yanze;Xie Xiangjun;Wang Ying;Qi Rui;Yang Ruihua(Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Military Medical University, Xi＇an 710032, China)

机构地区：[1]第四军医大学预防医学系营养与食品卫生学教研室,西安710032

出　　处：《神经解剖学杂志》2018年第2期230-236,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81271194)

摘　　要：目的:研究DHA对糖尿病认知障碍大鼠空间学习记忆的作用,探讨DHA对糖尿病大鼠海马神经元SDF-1/CXCR4表达的影响。方法:采用SD大鼠,随机分为对照组、对照+DHA组、糖尿病组和糖尿病+DHA组,以高脂膳食加小剂量链脲佐菌素诱发大鼠糖尿病。Morris水迷宫检测大鼠空间学习记忆能力,ELISA法、PCR法检测海马神经元SDF-1、TNF-α含量,免疫组化法检测CXCR4受体表达情况,Western Blot法检测海马神经元JNK磷酸化水平。结果:DHA可在一定程度上改善糖尿病大鼠学习记忆能力。糖尿病大鼠海马神经元TNF-α和p-JNK水平升高,SDF-1水平明显降低,CXCR4受体阳性神经元数量明显减少。DHA抑制TNF-α和JNK磷酸化,增加CXCR4的表达,升高SDF-1的含量。结论:DHA可减轻糖尿病大鼠的认知损伤,其机制可能与提高SDF-1水平,抑制海马神经元JNK磷酸化,降低炎性因子水平有关。Objective： To study the effect of DHA on learning and memory in diabetic rats and to investigate the effect of DHA on the expression of SDF-1/CXCR4 in hippocampal neurons of diabetic rats. Methods： Sprague-Dawley rats were randomly divided into Control,Control ＋ DHA,Diabetic and Diabetic ＋ DHA groups. The model of diabetes was induced by high fat diet and low dose of streptozotocin injection. Learning and memory were evaluated by Morris Water Maze. The levels of SDF-1 and TNF-α were detected by ELISA and PCR. Immunohistochemistry staining was used to detect the expression of CXCR4 and Western Blot was used to detect the phosphorylation of JNK. Results： DHA effectively improved learning and memory impairments in diabetic rats. TNF-α and p-JNK increased and SDF-1 decreased in diabetic rats. CXCR4 positive neurons in diabetic rats were significantly decreased. DHA inhibited the TNF-α and phosphorylation of JNK and increased the expression of CXCR4 and SDF-1 level. Conclusion： DHA can effectively attenuate the cognitive impairments in diabetic rats,which may be due to the increasing of SDF-1 and inhibition of JNK phosphorylation and decreasing inflammatory cytokines.

关 键 词：糖尿病 海马神经元 二十二碳六烯酸 基质细胞衍生因子1 C-JUN氨基末端激酶 

分 类 号：R587.2[医药卫生—内分泌]