Network Pharmacology Combined with circRNA to Study the Pharmacodynamic Mechanism of Liangxue Tongyu Prescription in Intervening in the Acute Phase of Intracerebral Hemorrhage
Objective To explore the therapeutic mechanism of Liangxue Tongyu Prescription in the treatment of acute Intracerebral hemorrhage by studying the target of Liangxue Tongyu Prescription on circRNAand possible related signaling pathways in Spontaneously hypertensive rats(SHR)in the acute stage of Intracerebral hemorrhage.Methods The SHR was divided into model group,experimental group and blank group.Intracerebral hemorrhage models were performed in model group and experimental group,the neurological deficits of SHR were scored.The experimental group was given Liangxue Tongyu Prescription for 5 days,the model group and the blank group were given equal doses of normal saline for 5 days each.The circRNA in the three groups of SHR brain tissue samples were detected by high-throughput sequencing technology,and the significantly different circRNAs were analyzed by Cluster Analysis,Go and KEGG enrichment analysis.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to verify the expressions of the top 5 significantly different circRNAwith fold change.The significantly differentially expressed circRNA were transformed into human homologous genes,and combined with the treatment targets selected by our research group in the early stage of Intracerebral hemorrhage,the intersection targets were input into Cytoscape software to construct the traditional Chinese medicines-components-targets-pathways network.Results The results of sequencing showed that there were 150 significantly different circRNA,including 60 up-regulated circRNAand 90 down-regulated circRNA.RT-PCR verification results showed that the expression trends of the top 5 circRNA were consistent with the high-throughput sequencing results.Network pharmacology results show that multiple active ingredients in six traditional Chinese medicines including Radix Paeoniae Rubra,Rheum officinale,Rehmannia glutinosa,Paeonia suffruticosa,Acorus tatarinowii and Panax notoginseng in Liangxue Tongyu Prescription correspond to the acute phase treatment target PRKCA of Intracerebral hemorrhage,which is the parent gene of CIRI_circ_10530.Among 849 GO enrichment entries,the parent gene of CIRI_circ_10530 was distributed in 209 GO terms;Among 149 KEGG signal pathways,the parent gene of CIRI_circ_10530 was distributed in 62 signal pathways.And Rheum officinale is the important Chinese medicine in Liangxue Tongyu Prescription for the treatment of acute Intracerebral hemorrhage.Kaempferol,emodin and quercetin are important active components of the pharmacodynamic mechanism of Liangxue Tongyu Prescription.Conclusion The mechanism of Liangxue Tongyu Prescription in the acute phase of Intracerebral hemorrhage may be related to the activation of PRKCA by kaempferol,quercetin,emodin and other key active ingredients,and the regulation of PKC affecting its key signaling pathways.
Liangxue Tongyu PrescriptionAcute phase of Intracerebral hemorrhagecircRNANetwork pharmacologyTranscriptomics
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