摘要
目的探讨白藜芦醇(RL)对糖尿病大鼠认知和记忆功能的影响及使海马CA1区域神经元细胞形态学的改变,分析Wnt通路的作用。方法36只Wistar鼠随机分为糖尿病组(DM组)、RL组及正常对照(NC)组,每组各12只。腹腔注射STZ建立糖尿病模型,RL组行8周RL灌胃。通过新物体识别实验和定位实验评估大鼠非空间及空间认知能力;病理切片TUNEL染色观察大鼠海马CA1区域神经元细胞形态学改变;Western blot检测海马组织Wnt通路凋亡相关蛋白表达水平。结果RL干预逆转DM组新物体及新位置分辨指数的下调[(44.71±11.21)%vs(1.57±0.39)%,(28.01±5.37)%vs(3.73±1.07)%,P<0.05],降低海马CA1区域TUNEL阳性神经元密度[(20.4±2.65)vs(47.0±4.58)个/mm2,P<0.05];RL干预逆转DM组海马CA1区域细胞Wnt-3、TGF-1、Bax、caspase-3蛋白表达上调,Bcl-2表达下调;上调脑源性神经营养因子表达(P<0.05)。结论RL具有Wnt通路抑制作用,可促进神经营养因子分泌,减少神经细胞凋亡,改善糖尿病大鼠非空间及空间认知能力。
ObjectiveTo investigate the effect of resveratrol(RL)on cognition in diabetic rats and the morphological changes of neurons in the hippocampal CA1 region,and to analyze the role of Wnt pathMethodsDiabetes mellitus(DM)model was established using Wistar rats with intraperitoneal injection of streptozotocin(STZ). RL group was given a RL lavage for 8 weeks. Rat spatial and non-spatial learning ability was evaluated by novel object/object location tasks. The morphological changes of neurons in the hippocampal CA1 region in rats were evaluated by TUNEL staining. The expressions of Wnt pathway and apoptosis related protein in hippocampus were detected by Western blot.Results could reverse the decrease of new object and new position discrimination index in DM group[(44. 71 ±11. 21)% vs(1. 57±0. 39)%,(28. 01±5. 37)% vs(3. 73±1. 07)%,P<0. 05]. The density of TUNEL positive neurons in the hippocampus CA1 was significantly higher in DM group than in NC group,and could be reduced by RL intervention[(20. 4±2. 65)vs(47. 0±4. 58)n/mm2,P<0. 05]. Expression of Wnt-3,TGF-1,Bax and caspase-3 were up-regulated,whereas Bcl-2 and BDNF were down-regulated in rat hippocampal CA1 region in DM group. RL intervention significantly reversed this status and up-regulated the expression of BDNF(P<0. 05).ConclusionRL inhibited Wnt pathway,promoted the secretion of neurotrophic factor and reduced the apoptosis of nerve cells,thus improving the spatial and non-spatial cognition of diabetic rats.
作者
程晶
游剑虹
CHENG Jing;YOU Jianhong(Department of Clinical Medicine,Quanzhou Medical College,Quanzhou 362000,China)
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2020年第5期379-383,共5页
Chinese Journal of Diabetes
基金
福建省中青年教师教育科研项目(JAT171162)。
关键词
糖尿病
认知功能
白藜芦醇
海马
WNT通路
Diabetes mellitus
Cognitive function
Resveratrol
Hippocampus
Wnt pathway
