Background: Cerebral ischemia-reperfusion injury (CI/R) is among the mast common diseases affecting the central nervous system. Due to the poor efficacy and adverse side effects of the drugs used to treat CUR in clinical trials, a new treatment strategy is urgently needed. In this study, we aimed to investigate whether miR-103a-3p alleviates CI/R in vivo and vitro and to explore the relevant mechanisms. Methods: BV2 microglial cells underwent oxygen-glucose deprivation (OGD) treatment to imitate the pathophysiology of CI/R in vitro. A middle cerebral artery occlusion (MCAO) rat model was established to imitate the pathophysiology of CI/R in vivo. The expression levels of miR-103a-3p and HMGB1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) and Nissl staining were used to evaluated apoptosis, oxidative stress, inflammatory response, and histopathology, respectively. Results: OGD-stimulated BV2 microglial cells and brain tissues with Cl/R had low expression of miR-103a-3p but high expression of high mobility group box 1 (HMGB1). As expected, miR-103a-3p and HMGBI had a targeting relationship. Overexpression of HMGBI enhanced the the levels of interleukin (IL)- I beta, tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA), but reduced the content of superoxide dismutase (SOD), IL-4, and IL-10, in vitro. Moreover, high expression of HMGB1 aggravated the brain injury of the model rats, and increased the secretion of inflammatory factors, exacerbated oxidative stress, and further induced tissue apoptosis in the brain tissue. Importantly, these effects of HMGBI overexpression were partly reversed by miR-103a-3p overexpression on HMGB1 interference. Conclusions: HMGB1 is targeted by miR-103a-3p, which may be a new strategy in the treatment of CI/R.
