The relationship between inflammasomes and the endoplasmic reticulum stress response in the injured spinal cord
The relationship between inflammasomes and the endoplasmic reticulum stress response in the injured spinal cord
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DOI：
10.1016/j.neulet.2019.04.033
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发表时间：
2019-07
影响因子：
2.5
通讯作者：
S. Yanagisawa;H. Katoh;Takeshi Imai;S. Nomura;Masahiko Watanabe
中科院分区：
文献类型：
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作者：
S. Yanagisawa;H. Katoh;Takeshi Imai;S. Nomura;Masahiko Watanabe
研究设计动物实验。目的研究炎性小体对大鼠脊髓损伤模型的影响。日本神奈川大学实验室。方法采用IH冲击器建立雌性SD大鼠胸部挫伤脊髓损伤模型，分为中度损伤组(LI)和重度损伤组(HI)。以假手术组为对照，于伤后不同时间点取出损伤脊髓，用免疫组织化学和免疫印迹法检测损伤脊髓炎性小体成分蛋白的表达。结果免疫印迹分析显示，脊髓损伤后炎性小体成分蛋白亮氨酸富含重复蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)和Caspase-2的表达较假手术组明显增加。硫氧还蛋白相互作用蛋白(TXNIP)是内质网应激诱导的一种激活NLRP3炎性小体的蛋白，在脊髓损伤动物中也显著升高。免疫组织化学显示脊髓损伤组少突胶质前体细胞(OPC)NLRP3、ASC和Caspase-2的表达明显高于SCI组星形胶质细胞和假手术组OPC。结论脊髓损伤后炎症体成分蛋白表达增加与内质网应激增加有关。OPC的炎症体蛋白水平明显高于星形胶质细胞，这可能与脊髓损伤后OPC细胞的高死亡率有关。
Study DesignAnimal study.ObjectivesThe aim of this study is to investigate the influence of inflammasomes in the injured spinal cord of a rat spinal cord injury model.SettingUniversity laboratory in Kanagawa, Japan.MethodsA thoracic contusion spinal cord injury (SCI) was induced in female Sprague Dawley rats using an IH-impactor to create a moderate injury group (LI) and a severe injury group (HI). Using a sham group as a control, the injured spinal cords were removed at several time points after injury to evaluate the levels of inflammasome component proteins in the injured spinal cord by immunohistochemistry and Western Blot.ResultsWestern blot analyses revealed that the expression of inflammasome component proteins leucine-rich repeat protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-2 significantly increased in the SCI animals compared to the sham animals. Thioredoxin interacting protein (TXNIP), which is a protein induced by ER stress that activates the NLRP3 inflammasome, was also significantly higher in the SCI animals. Immunohistochemistry revealed significantly higher expression of NLRP3, ASC, and Caspase-2 in oligodendrocyte progenitor cells (OPCs) of the SCI groups compared to astrocytes of the SCI groups and OPCs of the sham group.ConclusionsInflammasome component protein expression increases after SCI in association with increased ER stress. OPCs had significantly higher levels of inflammasome proteins compared to astrocytes, which may be associated with the high rates of OPC cell death after SCI.