摘要
目的:研究左归降糖解郁方通过调控Wnt3a/β-catenin信号通路改善糖尿病并发抑郁症大鼠海马神经发生的作用机制。方法:选取SPF级雄性SD大鼠40只建立糖尿病并发抑郁症大鼠模型,随机分为模型组、二甲双胍+氟西汀组(阳性药组)、左归降糖解郁方组(中药组)、左归降糖解郁方+DKK-1组(中药+DKK-1组),每组10只,另设10只大鼠为正常组。给药4周后,检测各组大鼠的血糖。采用强迫游泳实验和水迷宫实验检测各组大鼠的抑郁样行为和认知功能。采用免疫荧光法检测各组大鼠海马齿状回Nestin、DCX和NeuN的表达。采用Western blot法检测海马神经发生相关蛋白以及Wnt3a/β-catenin信号通路蛋白的表达。结果:与模型组比较,中药组血糖显著降低(P<0.01),抑郁样行为和认知能力显著改善(P<0.01,P<0.05),显著增加海马齿状回Nestin、DCX和NeuN的表达(P<0.05,P<0.01),增加Ngn2、NeuroD1、Wnt3a、Dvl-1的蛋白表达以及β-catenin的核表达(P<0.01),降低APC蛋白表达(P<0.05);与中药组比较,中药+DKK-1组大鼠海马Nestin、DCX、NeuN、Ngn2、NeuroD1、Wnt3a、Dvl-1及β-catenin表达显著减少(P<0.05,P<0.01)。结论:左归降糖解郁方可通过调节海马Wnt3a/β-catenin信号通路改善糖尿病并发抑郁症大鼠海马齿状回的神经发生过程。
Objective:To study the mechanism of Zuogui Jiangtang Jieyu Decoction(ZJJD)on Wnt3a/β-catenin signaling pathway in improving hippocampal neurogenesis in diabetic rats with depression.Methods:Forty SPF grade male SD rats were established as diabetic rats with depression model and randomly divided into model group,fluoxetine+metformin group,ZJJD group,ZJJD+DKK-1 group,10 in each one;Ten healthy rats were set as normal group.After 4 weeks of administration,the fasting blood glucose of rats were measured.The depression like behavior and cognitive function of rats were detected by the forced swimming test and the water maze test.The expression of Nestin,DCX and NeuN in dentate gyrus of hippocampus were detected by immunofluorescence.Western blot was used to detect the proteins related to hippocampal neurogenesis and Wnt3a/β-catenin signaling pathway.Results:Compared with the model group,ZJJD group significantly reduced the blood glucose(P<0.01)and improved the depression like behavior and cognitive function(P<0.01,P<0.05).ZJJD group significantly increased the expressions of Nestin,DCX(P<0.05,P<0.01),increased NeuN,Ngn2,NeuroD1,Wnt3a and Dvl-1 protein expression,as well as the nuclear expression ofβ-catenin(P<0.01),decreased the APC protein expression(P<0.05).Compared with ZJJD group,the expression of Nestin,DCX,NeuN,Ngn2,NeuroD1,Wnt3a,Dvl-1 andβ-catenin were significantly decreased in ZJJD+DKK-1 group(P<0.05,P<0.01).Conclusion:ZJJD can regulate Wnt3a/β-catenin signaling pathway in dentate gyrus of hippocampus,which may be related to the function of improving the hippocampal neurogenesis in diabetic rats with depression.
作者
杨蕙
雷诗卉
李薇
刘检
杨益
孟盼
何娅娜
王华
王宇红
YANG Hui;LEI Shi-hui;LI Wei;LIU Jian;YANG Yi;MENG Pan;HE Ya-na;WANG Hua;WANG Yu-hong(Center for Medical Research and Innovation,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Technology Innovation Center,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第5期2519-2524,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.82174357)
湖南省自然科学基金项目(No.2020JJ3027)
湖南省卫生健康委科研课题(No.202102041447)
湖南中医药大学校级基金项目(No.2019XJJJ069)
湖南省中药粉体与创新药物研究省部共建国家重点实验室培育基地开放基金项目(No.21PTKF1006)。
