Differential mRNA expression profiles of supplemented Naotaifang in vascular dementia rats by microarray analyses / 中草药

ABSTRACT

Objective: To explore the molecular mechanism of the supplemented Naotaifang (sNTF) in the treatment of vascular dementia (VD), and the mRNA expression profiles of hippocampal tissue of VD model rats before and after the intervention of modified sNTF were investigated by microarray analysis. Methods: VD model was established by bilateral common carotid artery ligation. VD rats were treated with sNTF for 30 days. HE staining and Morris water maze were used to evaluate the therapeutic effect of sNTF. The mRNA expression profiles data of VD model rats before and after intervention of sNTF were obtained by Agilent mRNA expression chip. The significantly differentially expressed genes were screened by microarray analysis, and the protein-protein interaction (PPI) network was constructed. The biological processes and signaling pathways in which differentially expressed genes were mainly involved and analyzed by GO and pathway enrichment. Immunohistochemistry and qRT-PCR were used to verify the chip analysis results. Results: HE staining and Morris water maze experiments showed that VD rats showed cerebral ischemia, hippocampal neuron damage, and decreased spatial learning and memory function, but sNTF can partially reverse this trend. 469 differential expression genes were screened by microarray analysis, including 180 up-regulated genes and 289 down-regulated genes. IL6, FGF2, TNF, and IL1b may be the main pharmacodynamic targets of sNTF in the treatment of VD rats, and the results were verified by immunohistochemistry and qRT-PCR. GO and pathway enrichment analysis showed that these genes were closely related to biological processes such as inflammation and apoptosis, and these genes were mainly involved in the regulation of TNF signaling pathway, toll-like receptor signaling pathway and the apoptosis pathway. Conclusion: The results suggested that the therapeutic effect of DSS on AD involves multiple genes and pathways, and and inhibition of hippocampal neuroinflammation may be one of the important mechanisms of its anti-VD.