RESUMO
BACKGROUND In China, electroacupuncture (EA) is used to treat the symptoms of ischemic stroke. However, the mechanisms involved in the effects of EA in cerebral ischemia remain to be investigated. This study aimed to investigate the molecular mechanism underlying the effects of EA in a rat model of cerebral ischemia-reperfusion injury (CIRI) induced by middle cerebral artery occlusion (MCAO). MATERIAL AND METHODS Seventy-five male Sprague-Dawley rats were divided into five groups: the sham group (with sham surgery), the model group (the MCAO model), the EA group (treated with EA), the EA control group, and the EA+antagomir-223-3p group. Rats in the model of CIRI underwent MCAO for 90 minutes. EA was performed on the second postoperative day and was performed at the Waiguan (TE5) and Zusanli (ST36) acupoints. The rat brains were evaluated for structural and molecular markers. RESULTS EA treatment significantly upregulated the expression of microRNA-223 (miR-223), NESTIN, and NOTCH1, and downregulated the expression of PTEN in the subventricular zone (SVZ) and hippocampus. The luciferase reporter assay supported that PTEN was a direct target of miR-223, and antagomiR-223-3p reversed the effects of EA and reduced the increase in NESTIN and inhibition of PTEN expression associated with EA treatment. There was a negative correlation between PTEN expression and the number of neural stem cells (NSCs). CONCLUSIONS In a rat model of CIRI following MCAO, EA activated the NOTCH pathway, promoted the expression of miR-223, increased the number of NSCs, and reduced the expression of PTEN.
Assuntos
Isquemia Encefálica/etiologia , Isquemia Encefálica/terapia , Eletroacupuntura , Infarto da Artéria Cerebral Média/complicações , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/terapia , Animais , Antagomirs/farmacologia , Sequência de Bases , Isquemia Encefálica/genética , Hipocampo/patologia , Masculino , MicroRNAs/genética , Nestina/metabolismo , Neuroproteção , Ratos Sprague-Dawley , Receptores Notch/genética , Receptores Notch/metabolismo , Traumatismo por Reperfusão/genética , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND Electroacupuncture (EA) has been commonly used to treat stroke in China. However, the underlying mechanism remains largely unknown. The present study investigated the neuroprotective effects of EA in middle cerebral artery occlusion (MCAO) rats and elucidated the possible anti-inflammatory mechanisms. MATERIAL AND METHODS In this study, modified neurological severity scoring (mNSS) was used to assess neurological deficits, and TTC staining and brain water content were measured to evaluate the degree of brain damage. HE staining, Nissl staining, and TUNEL staining were employed to evaluate apoptotic neuronal death. Molecular biological methods were used to measure the levels of miR-233, NLRP3, caspase-1, IL-1ß, and IL-18 in the peri-infarct cortex. RESULTS Our results showed that EA treatment significantly decreased the neurological deficit score and infarct volume of MCAO rats. The level of miR-223 was increased, while the levels of NLRP3, caspase-1, IL-1ß, and IL-18 were decreased in the peri-infarct cortex of EA-treated MCAO rats. However, the neuroprotective effect of EA was partially blocked by antagomir-223. CONCLUSIONS These data suggest that EA treatment can alleviate neuroinflammation by inhibiting the miR-223/NLRP3 pathway, thus playing a neuroprotective role in MCAO in rats.