抑制IRE1α/NF-κB通路减轻蛛网膜下腔出血后炎症反应

Inhibition of IRE1α/NF-κB Pathway Alleviates Inflammatory Response after Subarachnoid Hemorrhage

摘要: 目的：探讨肌醇激酶-1 (IRE1α)/核因子κB (NF-κB)通路与蛛网膜下腔出血(SAH)炎症反应的关系。方法：通过血管内穿刺法建立SAH模型。所有实验动物随机分为Sham组、SAH组、SAH + DMSO组、SAH + STF-083010 (IRE1α抑制剂)组、SAH + BAY11‐7082 (NF-κB抑制剂)组。使用改良加西亚评分评估神经功能。蛋白免疫印迹法(Western blot)检测IRE1α、葡萄糖调节蛋白78 (GRP78)、NF-κB的表达。采用酶联免疫吸附测定(ELISA)试剂盒检测炎症因子(TNF-α、IL-1β和IL-6)的浓度。结果：SAH后改良加西亚评分降低，IRE1α、GRP78、NF-κB蛋白表达和炎症因子(TNF-α, IL-1β, IL-6)表达均增加，抑制IRE1α/NF-κB通路后所有结果正好相反。皮尔森相关分析显示炎症因子表达与改良加西亚评分呈负相关。结论：抑制IRE1α/NF-κB通路可以减轻SAH后炎症，发挥神经保护作用。

Abstract: Objective: To investigate the role of IRE1α/NF-κB pathway in promoting the inflammatory response of subarachnoid hemorrhage (SAH); To investigate the relationship between Inositol Requiring En-zyme1α (IRE1α)/nuclear factor-κB (NF-κB) pathway and inflammatory response in subarachnoid hemorrhage (SAH). Methods: The model of SAH was established by intravascular puncture. All the animals were randomly divided into Sham group, SAH group, SAH + DMSO group, SAH + STF-083010 (IRE1α inhibitor) group, and SAH + BAY11‐7082 (NF-κB inhibitor) group. Neurological function was assessed using the modified Garcia score. The expressions of IRE1α, GRP78 and NF-κB were detected by Western blot. The concentrations of inflammatory cytokines (TNF-α, IL-1β and IL-6) were determined by ELISA kit. Results: The modified Garcia score decreased, the expression of GRP78, IRE1α, NF-κB and inflammatory cytokines increased after SAH, whereas their results were reversed since the inhibition of IRE1α/NF-κB pathway. Correlation analysis showed that the ex-pressions of inflammatory cytokines were negatively correlated with the modified Garcia score. Conclusion: Inhibition of IRE1α/NF-κB pathway can reduce inflammation and provide neuroprotec-tion after SAH.