Abstract
MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs. Recent research has proven that miRNAs play an essential role in the occurrence and development of ischemic stroke. Our previous studies confirmed that 20(R)-ginsenosideRg3 [20(R)-Rg3] exerts beneficial effects on cerebral ischemia–reperfusion injury (CIRI), but its molecular mechanism has not been elucidated. In this study, we used high-throughput sequencing to investigate the differentially expressed miRNA and mRNA expression profiles of 20(R)-Rg3 preconditioning to ameliorate CIRI injury in rats and to reveal its potential neuroprotective molecular mechanism. The results show that 20(R)-Rg3 alleviated neurobehavioral dysfunction in MCAO/R-treated rats. Among these mRNAs, 953 mRNAs were significantly upregulated and 2602 mRNAs were downregulated in the model group versus the sham group, whereas 437 mRNAs were significantly upregulated and 35 mRNAs were downregulated in the 20(R)-Rg3 group in contrast with those in the model group. Meanwhile, the expression profile of the miRNAs showed that a total of 283 differentially expressed miRNAs were identified, of which 142 miRNAs were significantly upregulated and 141 miRNAs were downregulated in the model group compared with the sham group, whereas 34 miRNAs were differentially expressed in the 20(R)-Rg3 treatment group compared with the model group, with 28 miRNAs being significantly upregulated and six miRNAs being significantly downregulated. Furthermore, 415 (391 upregulated and 24 downregulated) differentially expressed mRNAs and 22 (17 upregulated and 5 downregulated) differentially expressed miRNAs were identified to be related to 20(R)-Rg3′s neuroprotective effect on stroke recovery. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 20(R)-Rg3 could modulate multiple signaling pathways related to these differential miRNAs, such as the cGMP-PKG, cAMP and MAPK signaling pathways. This study provides new insights into the protective mechanism of 20(R)-Rg3 against CIRI, and the mechanism may be partly associated with the regulation of brain miRNA expression and its target signaling pathways.
Highlights
Ischemic stroke is an acute cerebrovascular disease that has become seriously harmful to human health due to its high mortality, disability and recurrence rates [1]
Compared with the sham group, the total distance, the average speed of movement and the neurological score were significantly decreased in the model group, while these changes were significantly increased in comparison to the 20(R)-Rg3 group (p < 0.05 and p < 0.01, Figure 2A–D)
Cerebral ischemia–reperfusion injury is caused by the restoration of blood supply after cerebral tissue ischemia for a certain period of time
Summary
Ischemic stroke is an acute cerebrovascular disease that has become seriously harmful to human health due to its high mortality, disability and recurrence rates [1]. Ginsenosides are the active ingredients of Panax notoginseng, which has a long application history in East Asian nations such as China, Korea and Japan. It has various pharmacological effects, such as antiaging, anti-inflammatory and antitumor effects [6–8]. Studies have shown that a variety of miRNAs participate in the regulation of CIRI by affecting multiple signaling pathways, such as neuronal apoptosis, the inflammatory response and oxidative stress [14,15]. Transcriptomics is an emerging discipline focused on the regulation at the genomic and/or transcriptomic levels containing cells or tissues from animal to human and reveals the mechanism of gene expression regulation by studying the changes in the expression of all RNA, including miRNA [18].
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