An Intersectional Study of LncRNAs and mRNAs Reveals the Potential Therapeutic Targets of Buyang Huanwu Decoction in Experimental Intracerebral Hemorrhage

Abstract

Background/aims: Both experimental and clinical studies have revealed satisfactory effects of the traditional Chinese formula Buyang Huanwu decoction (BYHWD) in improving post-intracerebral hemorrhage (ICH) neurological deficiencies. However, the multifaceted mechanisms of BYHWD in ICH treatment are not comprehensively understood. The present study explored various therapeutic targets of BYHWD by using lncRNA and mRNA transcriptomics.

Methods: LncRNA and mRNA microarrays were used to identify differentially expressed genes. ICH-induced upregulated genes (ICH vs sham) and BYHWD-induced downregulated genes (BYHWD vs ICH) were first identified. The intersection between these 2 sets was determined to identify ICH-induced highly expressed genes that were reversed by BYHWD. Then, the genes downregulated after ICH and the genes upregulated after BYHWD treatment were used to generate another set of intersections. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were subsequently performed to determine relative biological functions and signaling transduction pathways according to genes within the intersections. Quantitative real-time PCR was used to validate changes in gene expression observed using the microarray. Finally, a lncRNA-mRNA co-expression network was established to identify links among the genes within the intersections.

Results: A total of 18 differentially expressed lncRNAs and 33 differentially expressed mRNAs were identified using 2 lncRNA arrays (ICH vs sham and BYHWD vs ICH). The altered genes were enriched in the hemoglobin complex, oxygen transport and oxygen transporter and were closely associated with pyruvate metabolism. The co-expression network consisted of 53 nodes and 595 connections (308 positive interactions and 287 negative interactions).

Conclusion: The hemoglobin complex, oxygen transport, oxygen transporter activity and pyruvate metabolism are possible therapeutic targets of BYHWD in ICH treatment. The present study provides the basis and direction for future investigations to explore the mechanisms by which BYHWD protects against long-term neurological deficiencies after ICH.

Keywords: Expression profile; Intersectional study; Intracerebral hemorrhage; Long non-coding RNA (lncRNA); Messenger RNA (mRNA).