Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis
Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis
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DOI：
10.1007/s12035-021-02506-7
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发表时间：
2021-08-09
影响因子：
5.1
通讯作者：
Kikuchi, Kiyoshi
中科院分区：
文献类型：
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作者：
Otsuka, Shotaro;Setoyama, Kentaro;Kikuchi, Kiyoshi
蛛网膜下腔出血（SAH）是一种灾难性的中风形式，导致显著的发病率和死亡率。氧化应激、炎症和神经元凋亡在SAH后早期脑损伤（EBI）的发病机制中起重要作用。预处理运动赋予神经保护作用，减轻EBI;然而，这种保护的基础是未知的。我们研究了预处理运动对SAH后脑损伤和感觉运动功能的影响。将雄性大鼠分为假手术组（Sham）、运动组（Ex）和非运动组（No-Ex）。经过3周的锻炼计划后，他们通过血管内穿孔接受了SAH。对意识水平、神经功能评分和感觉运动功能进行了研究。核因子红细胞2 p45相关因子2（Nrf 2）、血红素加氧酶1（HO-1）、4-羟基壬烯醛（4 HNE）、硝基酪氨酸（NT）、离子钙结合衔接分子1（Iba 1）、肿瘤坏死因子α（TNF α）的表达通过免疫组织化学或蛋白质印迹法评估肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）、白细胞介素1 β（IL-1 β）、14-3-3 γ、β-连环蛋白Ser 37、Bax和半胱天冬酶-3。还进行了末端脱氧核苷酸转移酶介导的生物素化dUTP缺口末端标记（TUNEL）试验。SAH后，与No-Ex组相比，Ex组的神经功能缺损、感觉运动功能障碍和意识障碍显著减少。Ex组中Nrf 2、HO-1和14-3-3 γ显著升高，而4 HNE、NT、Iba 1、TNF-α、IL-6、IL-1 β、Bax、caspase-3和TUNEL阳性细胞显著降低。我们的研究结果表明，预处理运动改善EBI后SAH。Nrf 2/HO-1通路的激活降低了4 HNE和NT的表达;此外，氧化应激和炎症均减少。此外，预处理运动可能通过14-3-3 γ/β-连环蛋白Ser 37/Bax/caspase-3途径减少细胞凋亡。
Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta), 14-3-3 gamma, p-beta-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14-3-3 gamma were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-alpha, IL-6, IL-1 beta, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14-3-3 gamma/p-beta-catenin Ser37/Bax/caspase-3 pathway.