广西医学2024，Vol.46Issue(11)：1698-1704,7.DOI:10.11675/j.issn.0253-4304.2024.11.11
丹参酮ⅡA对链脲佐菌素诱导阿尔茨海默病大鼠模型的干预作用及机制
Intervention effect of tanshinone ⅡA on streptozocin induced Alzheimer's disease in rats model and its mechanism
摘要
Abstract
Objective To analyze the intervention effect of tanshinone ⅡA on learning and memory dysfunction in Alzheimer's disease(AD)rats model induced by streptozocin(STZ),and to explore its possible mechanism.Methods(1)Effect targets of tanshinone ⅡA were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and targets related to AD were obtained through the databases of DisGeNET,GeneCards®,and OMIM®;in addition,the intersection targets of these two categories of targets were obtained by using the Venny 2.1 platform.The protein-protein interaction network of intersection targets was established and the core targets were screened by using the STRING database and Cytoscape 3.2.1 software.The enrichment analysis was performed on intersection targets by the DAVID database.(2)A total of 56 SD rats were randomly assigned to normal group,sham operation group,STZ group,donepezil group,or low-,medium-,and high-dose tanshinone ⅡA groups,with 8 rats in each group.Except for the normal group and the sham operation group,AD models of rats in the remaining groups were established through cerebral stereotaxic injection of STZ.On the second day after injection,rats of various administration group received intragastric administration of corresponding drugs.On the 23th and 24th day after injection,new object recognition experiment was performed for detecting learning and memory function of rats in various groups,and then mRNA expressions of interleukin(IL)-1β,IL-6,and brain-derived neurotrophic factor(BDNF)in hippocampus tissues were detected in various groups.Results(1)A total of 24 intersection targets were obtained,and 10 core targets containing MMP9,TP53,JUN,FOS,PTGS2,EDN1,MYC,RELA,Caspase-3,and NFKBIA were screened.The functional enrichment analysis indicated that the intersection targets mainly acted on cellular compositions such as organelle membrane,nucleus,and cell membrane,were involved in molecular functions in terms of regulated transcription factor binding,enzyme binding,and protease binding,etc.,participated in biological processes with respect to regulation of drug response and negative regulation of apoptosis,etc.,and were enriched in signaling pathways such as cyclic adenosine monophosphate(cAMP)signaling pathway and tumor necrosis factor(TNF)signaling pathway,neurotrophic factor signaling pathway,etc.(2)Compared with the sham operation and normal groups,rats of the STZ group obtained a decreased discrimination index,a down-regulated expression of BDNF mRNA,whereas up-regulated mRNA expressions of IL-1β and IL-6(P＜0.05).Compared with the STZ group,rats of various administrations groups obtained an elevated discrimination index,an up-regulated mRNA expression of BDNF,whereas down-regulated mRNA expressions of 1L-1β and IL-6(P＜0.05).There was no statistically significant difference in discrimination index and mRNA expressions of IL-1β and IL-6 between the administration groups with various tanshinone ⅡA doses and the donepezil group,and in BDNF mRNA expression between the high-dose tanshinone ⅡA group and the donepezil group(P＞0.05).Conclusion Tanshinone Ⅱ A can ameliorate learning memory and cognitive impairment of AD rats model induced by STZ,and its effect is similar to commonly used clinical drug donepezil.Tanshinone ⅡA can regulate cAMP and neurotrophic factors signaling pathway,and inhibit inflammatory factors,so as to exert effect through acting on multiple targets such as MMP9,TP53,JUN,FOS,and PTGS2.关键词
阿尔茨海默病/认知功能障碍/丹参酮ⅡA/链脲佐菌素/环磷酸腺苷信号通路/炎症反应/网络药理学/生物信息学Key words
Alzheimer's disease/Cognitive impairment/Tanshinone ⅡA/Streptozocin/Cyclic adenosine monophosphate signaling pathway/Inflammatory response/Network pharmacology/Bioinformatics分类
医药卫生引用本文复制引用
项锡勇,夏思雨,周怡俊,李珊,王俪璇,曾怡蓉,余佳佳,梁美,周燕..丹参酮ⅡA对链脲佐菌素诱导阿尔茨海默病大鼠模型的干预作用及机制[J].广西医学,2024,46(11):1698-1704,7.基金项目
国家自然科学基金(81660213、81360192) （81660213、81360192）
广西自然科学基金(2023GXNSFAA026160、2018GXNSFAA281325、2017GXNSFAA198187) （2023GXNSFAA026160、2018GXNSFAA281325、2017GXNSFAA198187）
长寿与老年相关疾病教育部重点实验室(自然科学类)(KLLAD202208) （自然科学类）
