| Background:Post-stroke depression(PSD)is considered as one of the most frequent psychiatric complications of stroke,About one-third of stroke survivors suffer from major depression after stroke.Depressive symptoms were most common in the first three to six months after stroke,and the prevalence of PSD remained high in the following years.As we all know,PSD has an important influence on the course,rehabilitation and prognosis of stroke.PSD has a negative impact on patients' ability to carry out rehabilitation treatment,which is closely related to the recovery of physical and cognitive function and the further deterioration of quality of life,and brings a heavy burden to the society and families.Therefore,the early and accurate diagnosis of PSD is very important and should be paid great attention by clinicians.Because the diagnosis of PSD is mainly based on patients' clinical manifestations and related scales,stroke patients are often characterized by neurological disorders,and their early depressive symptoms are easily ignored by doctors and their families.Moreover,the diversity of PSD affective disorders,the complexity of somatic symptoms of stroke patients,and scale evaluation are easily affected by patients' subjective factors.resulting in a high rate of missed diagnosis of PSD.Exosome is a special subtype of secretory membrane vesicles,which participates in cell-to-cell signal transmission by transferring exosome molecules including protein,mRNA and micro-RNA(miRNAs).At present,exosome micro-RNA can be used as a biomarker of acute cerebral infarction and epilepsy.However,the expression of serum exosome micro-RNA in PSD has not been reported.Therefore,the purpose of this study is to explore the clinical characteristics of PSD and the differential expression of exosome micro-RNA,to carry out preliminary bioinformatics analysis of differential exosome micro-RNA by GO and KEGG,and to further screen out specific exosome micro-RNA molecular markers in the later stage,and to develop new diagnostic markers and effective treatment of PSD has very important and far-reaching significance.Methods:1.Five hundred and eighty-three patients with Acute cerebral infarction,admitted to our hospital from May 2018 to December 2019 were assessed with Hamilton Depression Scale-17(HAMD-17)to evaluate the depression degrees.Finally,the 408 cases were included in the study.accordingly,they were divided into PSD group(n=162)and non-PSD group(n=246).2.The exosomes were separated from plasma of 10 patients with severe PSD and 10 patients without PSD by an RiboTM exosome Isolation reagent Kit.3.The RNA of the exosome were extracted by HiPure Exosome RNA Kit from PSD and non-PSD.4.High-throughput sequencing of RNA extracted from two groups by high-throughput sequencer.5.The differentially expressed miRNA of two groups were analyzed by DESeq.6.The target genes of differentially expressed miRNAs were predicted by TargetScan,miRDB,miRTarBase and miRWalk.7.Functional annotation and pathway enrichment analysis of differentially expressed miRNAs target genes were performed by GO and KEGG,respectively,in order to further understand the biological function of exocrine micro-RNAs differentially expressed between PSD and non-PSD patients.Results:1.The expression profiles of serum exocrine miRNAs in PSD group and non-PSD group were constructed by high-throughput sequencing,and a total of 240 miRNAs were identified.Among them,78 miRNAs expressions were up-regulated(among which 11 had a fold change of>4 times?among which 2 had a fold change of>6 times)and 162 miRNAs expressions were down-regulated(among which 18 had a fold change of>4 times?among which 4 had a fold change of>6 times).2.Four software(TargetScan?miRDB?miRTarBase?miRWalk)were used to predict target gene of the first obviously different 6 miRNAs between the two groups,and 390 target genes were obtained totally.GO and KEGG analysis of these target genes were made,and the biological process annotation of the main enrichment of these target genes is the regulation of biological process?regulation of cellular process?cellular macromolecule metabolic process?regulation of cellular metabolic process?regulation of metabolic process etc.The Cellular Component annotation of the main enrichment of these target genes is intracellular membrane-bounded organelle?organelle?cytoplasm etc.The Molecular Function annotation of the main enrichment of these target genes is protein binding?DNA binding?nucleic acid binding?regulatory region nucleic acid binding?regulatory region DNA binding?transcription regulatory region DNA binding?sequence-specific DNA binding.Furthermore,KEGG pathway analysis of differentially expressed miRNAs gene profiles showed 15 signaling pathways involving differentially expressed up-regulated miRNAs.Among these pathways,the signal pathways of the main enrichment of these target genes is Metabolic pathways?Insulin signaling pathway?Sphingolipid signaling pathway?Glycerophospholipid metabolism?Glycerolipid metabolism?Sphingolipid metabolism?Transcriptional misregulation in cancer etc.KEGG pathway analysis of differentially expressed miRNAs gene profiles showed 30 signaling pathways involving differentially expressed down-regulated miRNAs.Among these pathways,the signal pathways of the main enrichment of these target genes is AMPK signaling pathway?Regulation of actin cytoskeleton?Rap1 signaling pathway?HIF-1 signaling pathway?MicroRNAs in cancer?Signaling pathways regulating pluripotency of stem cells?PI3K-Akt signaling pathway?FoxO signaling pathway?Ras signaling pathway?Focal adhesion?Proteoglycans in cancer?Cell cycle?Endocytosis?Pathways in cancer?MAPK signaling pathway etc.Conclusions:1.240 kinds of obviously different exosomal miRNAs were screened out inPSD and non-PSD,which has provided a basis for studies new noninvasive diagnostic methods and new diagnostic markers.2.There is differential expression of miRNAs in the PSD and non-PSD,suggesting that lncRNA might be involved in the regulation of the development and progression of PSD,which will provide an experimental basis for further studies.Figure 18 table 7 reference 64... |
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