RESUMO
Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.
Assuntos
Biomarcadores , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Panax notoginseng/química , Traumatismo por Reperfusão/etiologia , Animais , Biópsia , Biologia Computacional/métodos , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Ratos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/tratamento farmacológico , Roedores , Transdução de Sinais , TranscriptomaRESUMO
Treatment with Panax notoginseng saponin (PNS) can prevent neurological damage in middle cerebral artery occlusion model rats to promote recovery after a stroke. However, the exact molecular mechanisms are unknown and require further study. In the present study, mRNA sequencing was employed to investigate differential gene expression between model and sham groups, and between model and PNStreated groups. Enrichment of gene data was performed using Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes database. Hub genes were identified and networks were constructed using Cytoscape that were further verified by reverse transcriptionquantitative PCR. A total of 1,104 genes of interest were found, which included 690 upregulated and 414 downregulated genes that were identified when the model was compared with the sham group. Additionally, 817 genes of interest, which included 390 upregulated and 427 downregulated genes, were identified when the PNStreated group was compared with the model group. There were 303 overlapping genes of interest between the analysis of model to sham groups, and the analysis of model to PNStreated groups. The top 10 genes from the 303 aberrantly expressed genes of interest included ubiquitin conjugating enzyme E2 variant 2, small ubiquitinrelated modifier 1, small RNA binding exonuclease protection factor La, FinkelBiskisReilly murine sarcoma virus (FBRMuSV) ubiquitously expressed, centrosomal protein 290 kDa, DNAdirected RNA polymerase II subunit K, cullin4B, matrin3 and vascular endothelial growth factor receptor 2. In conclusion, these genes may be important in the underlying mechanism of PNS treatment in ischemic stroke. Additionally, the present data provided novel insight into the pathogenesis of ischemic stroke.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , AVC Isquêmico/tratamento farmacológico , Saponinas/farmacologia , Animais , Isquemia Encefálica/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes/genética , Sequenciamento de Nucleotídeos em Larga Escala , Infarto da Artéria Cerebral Média/patologia , AVC Isquêmico/genética , Masculino , Panax notoginseng/metabolismo , Raízes de Plantas/genética , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia , Transcriptoma/genéticaRESUMO
Central nervous system (CNS) inflammation occurs in cognitive dysfunctions, but the underlying mechanisms remain unclear. Here, we investigated the role of sirtuin 1 (SIRT1) and salidroside in CNS inflammation-induced cognitive deficits model. In vivo, CNS inflammation was initiated by a single intracerebroventricular injection of lipopolysaccharide (LPS). The levels of inflammatory cytokines and the capability of free radial scavenging were determined after the LPS challenge. In vivo, salidroside and nicotinamide, a SIRT1 inhibitor, were used in PC12 cell. Of note, with the treatment of salidroside, LPS-induced learning and memory impairments were effectively improved. Salidroside also remarkably inhibited the inflammatory cytokines, up-regulated the concentration of superoxide dismutase and inhibited the vitalities of malondialdehyde in serum, hippocampus, and cell supernatant. Besides, the expression of Sirt1, Nrf-2, HO-1, Bax, Bcl-2, caspase-9, and caspase-3 and the phosphorylation of AMPK, NF-κBp65, and IκBα were increased accompanying with the LPS-induced cognitive impairments, which were significantly suppressed by salidroside treatment. In PC12 cell model, nicotinamide significantly abrogated the beneficial effects of salidroside, as indicated by the antioxidant, anti-inflammatory, and antiapoptosis signaling. Together, our results showed that salidroside may be a novel therapy drug in neurodegenerative diseases, and the protective effect was involved in SIRT1-dependent Nrf-2/HO-1/NF-κB pathway.