摘要
目的探讨中药复方益糖康对db/db小鼠认知缺陷的改善以及可能的机制。方法选取24只db/db小鼠和8只db/m小鼠,随机分为四组:正常对照组(db/m组)、模型组(db/db组)、益糖康组(YTK组)以及西药(选用利拉鲁肽Liraglutide)对照组(LIRA组)。首先对小鼠空腹血糖(FBG)、血清胰岛素水平(FINS)和胰岛素抵抗指数(HOMA-RI)进行观察;通过Morris水迷宫任务和旷场实验对小鼠进行行为学检测;采用Nissl染色观察海马神经元Nissl小体数量,western blot检测突触后致密物质95(PSD 95)、突触素(SYN)以及脑源性神经营养因子(BDNF)蛋白观察海马的突触可塑性;通过透射电镜观察线粒体超微形态,免疫双标共染Cox1/Cox4观察线粒体功能变化,同时免疫荧光和western blot检测海马GPX 4、SLC7A11及Nrf 2蛋白的表达观察铁死亡。结果与db/m组相比,db/db组小鼠FBG、FINS和HOMA-RI明显升高;水迷宫和旷场实验等行为学功能显著下降,Nissl小体形态及数量异常,同时PSD 95、SYN及BDNF蛋白表达量明显降低;海马神经元线粒体结构异常,Cox1、GPX 4、SLC7A11及Nrf 2表达明显下降,Cox4表达上升。与db/db组相比,LIRA组及YTK组FBG、FINS和HOMA-RI明显下降;两组水迷宫均有明显改善,YTK组旷场实验改善更为明显,同时两组小鼠Nissl小体及PSD 95、SYN和BDNF蛋白表达均有回升;两组小鼠海马神经元线粒体结构均有改善,Cox1、GPX 4、SLC7A11及表达明显上升,Cox4表达下降,YTK组Nrf 2表达升高,但LIRA组Nrf 2表达无统计学意义。结论中药复方益糖康可以改善神经和突触可塑性损伤,保护认知功能,其机制可能是通过上调Nrf 2提高SLC7A11和GPX 4表达,改善线粒体结构和功能,抑制铁死亡。
Objective To investigate whether the Chinese herbal formula Yitangkang could improve cognitive deficits and possible mechanisms in db/db mice.Methods 24 db/db mice and 8 db/m mice were divided into normal group(db/m),model group(db/db),Yitangkang group(YTK)and Liraglutide group(LIRA).First,the mice were examined for fasting blood glucose(FBG),serum insulin(FINS)levels and Homeostasis model assessment-insulin resistance index(HOMA-RI);The Morris water maze test and open field test were used to behaviorally examine the mice;Synaptic plasticity and neuronal morphology in the hippocampus were observed by Nissl staining and PSD 95,SYN,and BDNF protein were detected by western blot;Mitochondrial ultrastructure was assessed by transmission electron microscopy;Cox1/Cox4 was co-stained by immunofluorescence,while the hippocampal expression of GPX 4,SLC7A11,and Nrf 2 were examined by immunofluorescence and western blot to detect ferroptosis.Results Compared with the db/m group,the FBG,FINS and HOMA-RI in the db/db mice were significantly increased;The functions of water maze test and openfield test were significantly decreased;The morphology and quantity of Nissl body were abnormal;The expression of PSD95,SYN and BDNF proteins decreased significantly;The mitochondrial structure of hippocampal neurons was damaged;The expressions of Cox1,GPX 4,SLC7A11 and Nrf 2 decreased significantly,with the expression of Cox4 increased.Compared with the db/db group,the FBG,FINS and HOMA-RI of the LIRA group and YTK group were significantlydecreased;The water maze test for these two groups was significantly improved;The open field test for the YTK groupimproved more significantly;The number of Nissl body and the expressions of PSD 95,SYN and BDNF proteinsincreased;The mitochondrial structure of hippocampal neurons in the two groups of mice improved;The expression ofCox1,GPX 4 and SLC7A11 increased significantly,and the expression of Cox4 decreased.The expression of Nrf 2protein in the YTK group increased,but the expression of Nrf 2 in the LIRA group was not statistically significant.Conclusion Yitangkang formula can improve nerve and synaptic plasticity damage and protect cognitive function.Themechanism may be through upregulation of Nrf 2 to increase the expression of SLC7A11 and GPX 4,improvemitochondrial structure and function,and inhibit ferroptosis.
作者
安继仁
刘天宇
石岩
杨宇峰
An Jiren;Liu Tianyu;Shi Yan;Yang Yufeng(First Clinical College,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2022年第6期2309-2318,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
辽宁省委组织部辽宁省“兴辽英才计划”项目(XLYC1807145):基于组学特征谱的代谢综合征中医证候分型精准医学研究,负责人:杨宇峰。
关键词
糖尿病
认知障碍
中药复方益糖康
铁死亡
Diabetes mellitus
Cognitive impairment
Yitangkang Formula
Ferroptosis
