急性脑出血模型大鼠脑组织中差异表达基因测序的验证及功能分析.

BACKGROUND: There are differentially expressed genes in acute intracerebral hemorrhage, which are related to the occurrence and development of intracerebral hemorrhage OBJECTIVE: To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage, to validate them through qPCR, and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS: Seventy-eight Sprague-Dawley rats were randomly divided into two groups: in intracerebral hemorrhage group, a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus; and in sham-operated group, rats were injected with equal amount of saline at the same site. RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage, which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage. And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION: Ten key genes were identified, including CXCL8, SERPINE1, TFPI2, CXCR4, GDA, KCNQ5, ERICH3, SCN3B, CACNA1E, and CCL20. The contents of GDA, KCNQ5, ERICH3, SCN3B, and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group (P < 0.05). The contents of CXCL8, SERPINE1, TFPI2, CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group (P < 0.05). The contents of GDA, KCNQ5, ERICH3, SCN3B, and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score (P < 0.05), while the contents of CXCL8, SERPINE1, TFPI2, CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score (P < 0.05). GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes (leukocyte chemotaxis and chemokine-mediated signaling pathways), two cell components (cation channel complexes and ion channel complexes), and two molecular functions (gated channel activity and ion channel activity). KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway, glutamatergic synapses and GABAergic synapses. To conclude, the differentially expressed genes in intracerebral hemorrhage include CXCL8, SERPINE1, TFPI2, CXCR4, GDA, KCNQ5, ERICH3, SCN3B, CACNA1E, and CCL20, and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage. These genes are mainly enriched in cell components, binding functions, cellular protrusions, and other related biological functions. [ABSTRACT FROM AUTHOR]