Exploration of the Molecular Mechanism of Wenpi Tongluo Kaiqiao Prescription in Treating Alzheimer's Disease Based on Mitochondrial Function

ZHANG Jinzhi; CHEN Wei; ZHUO Guifeng; ZHU Jianmin; CHEN Yuanliang; WU Lin

Abstract：Objective Based on bioinformatics,network pharmacology,immune infiltration analysis,machine learning and other methods,combined with experimental verification,the molecular mechanism of Wenpi Tongluo Kaiqiao prescription regulating mitochondrial function in the treatment of Alzheimer's disease(AD)was discussed.Methods The differentially expressed genes were obtained for correlation analysis,KEGG pathway enrichment analysis and immune infiltration analysis.After clustering and classifying the public data set samples,the differences of immune cells were analyzed,the machine learning model was constructed,the characteristic genes were screened and the risk prediction nomogram model was verified.The AD rat model was established,and water maze test,HE staining and RT-qPCR were performed to further verify the conclusion of data mining.Results DEGs interacted with each other,regulated the immune system and regulated the P53(tumor protein 53,p53)signaling pathway.The results showed that there were 13 differentially expressed genes,which were different from the distribution of immune cells in the subtypes.The best machine learning model was SVM,and the top 5 feature genes were MAOB,MAOA,CASP9,Bcl-2 and ABAT.The nomogram prediction model had high accuracy and low risk of prediction error.In animal experiments,the results showed that the learning and cognitive dysfunction and nerve injury in the Chinese medicine group were significantly reduced compared with the model group.The relative mRNA expressions of the characteristic genes were consistent with the results of data mining.Conclusion The mechanism of Wenpi Tongluo Kaiqiao prescription alleviating AD symptoms by regulating mitochondrial function may be based on the mutual network regulation,P53 signaling pathway and immune regulation of 13 different molecular targets.