Study On The Expression Of LncRNA,mRNA And MiRNA Of Yin And Yang Syndrome In Acute Ischemic Stroke

Objective:To study the difference of the expression of lncRNA?miRNA and mRNA in the serum of patients among Yin and Yang Syndrome with ischemic stroke and non-stroke subjects.Method:We use lncRNA/mRNA and miRNA microarrays to detect the expression of lncRNA,mRNA and miRNA in the serum of patients with ischemic stroke among Yin and Yang Syndrome and non stroke subjects.Difference expressed of LncRNAs and mRNAs in three groups were screened and analyzed.Cluster analysis of the differentially expressed genes,antisense lncRNA and mRNA co expression analysis,GO and KEGG functional pathway analysis were performed to obtain the intergenic regulation relationship and predict the target genes of lncRNA.At the same time,the selected part of lncRNA is verified by qRT-PCR.Result:1.We found 1023 lncRNAs?371 up-regulated and 752 down-regulated?and 587 mRNAs?288 up-regulated and 299 down-regulated?differently expressed in group of acute ischemic stroke.There are 6 pairs of antisense lncRNA and sense mRNA may have biological regulation mechanism in acute ischemic stroke:ENST00000428573?up-regulated?and SYT2?up?,ENST00000494849?cut?and PRKAR2B?up?,NR₀36505?down?and IPPK?down?,NR₁31907?up?and BCL2L1?up?,T071563?down?and CACNA1C(uc.148+?down?,and LRBA?down?.Stratified cluster analysis can distinguish the difference between lncRNA and mRNA in ischemic stroke and non stroke group.ENST00000530525,T029143 and T013651 were related to ischemic stroke verified by qRT-PCR.GO enrichment suggested that suggest differentially expressed mRNAs in acute ischemic stroke are mainly related to oxygen transport,white blood cells in the inflammatory migration,neurotransmitter secretion,negative regulation of Toll like receptor binding,histidine metabolism,uric acid metabolism.KEGG pathway analyzed revealed that capillary smooth muscle contraction,RAS signaling pathway,chemokine pathways,phospholipase D signaling pathway,platelet activation and leukocyte endothelial migration were involved.2.We found 257 lncRNAs?73 up-regulated and 154 down-regulated?,54 mRNAs?21 up-regulated and 33 down-regulated?,4 miRNAs?up-regulated?were differently expressed in the Yang Syndrome group;394 lncRNAs?283 up-regulated and 111 down-regulated?,206 mRNAs?177 up-regulated and 29 down-regulated?were differently expressed in the Yin Syndrome group.Cluster analysis reveal that the difference of lncRNAs,miRNAs and mRNAs expression profiles could distinguish Yin Syndrome and Yang syndrome samples;lncRNAs,mRNAs and miRNAs had differential expression in acute ischemic stroke patients between Yin Syndrome and Yang syndrome.There are 77 pairs of antisense lncRNA and mRNA that may be regulated in lncRNAs and mRNA between Yang Syndrome and Yin Syndrome.They may participate in the formation of syndrome patterns.GO and KEGG enrichment analysis suggested that differentially expressed mRNAs between Yin syndromes and Yang syndromes are mainly related to positive or negative regulation of blood pressure,notch receptors signaling pathway processes,aminobutyric acid/-A receptor complex and its activity,adrenergic receptor activity,arachidonic acid and its monooxygenase/epoxidase activity,negative regulation of interleukin 1/1?,respiratory outbreaks and other related.The pathway related to yang syndrome involved blood pressure regulation,which can explain the history of hypertension in Yang syndrome patients were more than in Yin syndrome patients in previous study.The excitatory adrenergic receptor pathway and the heterogeneous aminobutyric acid-related pathway are closely related to the different symptoms of yin and yang syndrome patients.Conclusion:There are obvious differences in transcriptome expression profiles between yin type syndrome and yang syndrome in patients with acute ischemic stroke.Diagnostic biomarkers for syndromes were founded.The occurrence and development of Yin and yang syndrome were related to inflammatory reaction,RAS System,platelet activation,neurotransmitter secretion and many other biological processes and key pathways.At the same time,we combined the differentially expressed antisense lncRNAs with differentially expressed sense mRNAs as potential mechanisms that play a role in the regulation of the pathogenesis of acute ischemic stroke.The difference between Yin syndrome and Yang syndrome is mainly reflected in positive/negative regulation of blood pressure,differential regulation of inhibitory neurotransmitters and excitatory neurotransmitters and related receptors,and inflammation and oxidative stress.It provides a scientific view for the study of the material basis and pathological mechanisms of the syndrome differentiation and treatment in Yin-Yang syndrome in acute ischemic stroke.