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Resveratrol reduces brain injury after subarachnoid hemorrhage by inhibiting oxidative stress and endoplasmic reticulum stress

    作者

    Xie, YK;Zhou, X;Yuan, HT;Qiu, J;Xin, DQ;Chu, XL;Wang, DC;Wang, Z

    作者单位

    [Xie, Yun-Kai; Zhou, Xin; Yuan, Hong-Tao; Qiu, Jie; Xin, Dan-Qing; Chu, Xi-Li; Wang, Da-Chuan] Shandong Univ, Sch Basic Med Sci, Dept Physiol, Jinan, Shandong, Peoples R China.;-;[Zhou, Xin; Wang, Zhen] Shandong Univ, Shandong Prov Hosp, Dept Spinal Surg, Jinan, Shandong, Peoples R China.

    摘要

    Previous studies have shown that resveratrol, a bioactive substance found in many plants, can reduce early brain injury after subarachnoid hemorrhage, but how it acts is still unclear. This study explored the mechanism using the experimental subarachnoid hemorrhage rat model established by injecting autologous blood into the cerebellomedullary cistern. Rat models were treated with an intraperitoneal injection of 60 mg/kg resveratrol 2, 6, 24 and 46 hours after injury. At 48 hours after injury, their neurological function was assessed using a modified Garcia score. Brain edema was measured by the wet-dry method. Neuronal apoptosis in the prefrontal cortex was detected by terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Levels of reactive oxygen species and malondialdehyde in the prefrontal cortex were determined by colorimetry. CHOP, glucose-regulated protein 78, nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 mRNA expression levels in the prefrontal cortex were measured by reverse transcription polymerase chain reaction. Tumor necrosis factor-alpha content in the prefrontal cortex was detected by enzyme linked immunosorbent assay. Immunohistochemical staining was used to detect the number of positive cells of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78, CHOP and glial fibrillary acidic protein. Western blot assay was utilized to analyze the expression levels of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78 and CHOP protein expression levels in the prefrontal cortex. The results showed that resveratrol treatment markedly alleviated neurological deficits and brain edema in experimental subarachnoid hemorrhage rats, and reduced neuronal apoptosis in the prefrontal cortex. Resveratrol reduced the levels of reactive oxygen species and malondialdehyde, and increased the expression of nuclear factor-erythroid 2-related factor 2, heme oxygenase-1 mRNA and protein in the prefrontal cortex. Resveratrol decreased glucose-regulated protein 78, CHOP mRNA and protein expression and tumor necrosis factor-alpha level. It also activated astrocytes. The results suggest that resveratrol exerted neuroprotective effect on subarachnoid hemorrhage by reducing oxidative damage, endoplasmic reticulum stress and neuroinflammation.

    关键词

    NEURONAL APOPTOSIS; RAT-BRAIN; PROTECTS; ANTIOXIDANT; PATHWAY; CELLS; MODEL; NEUROPROTECTION; DYSFUNCTION; ACTIVATOR
基本信息

  • 所属机构:

    归属医师:

    PMID:31169191

    UT:000470900400020

    刊名:NEURAL REGENERATION RESEARCH

    年,卷(期):2019年14卷10期

    页码:1734-1742

    DOI:10.4103/1673-5374.257529

    附件: other

    收录:   SCIE