Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice
Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice
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DOI：
10.1016/j.neuint.2021.105197
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发表时间：
2021-09-29
影响因子：
4.2
通讯作者：
Xie, Minjie
中科院分区：
文献类型：
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作者：
Tian, Yeye;Yuan, Xiao;Xie, Minjie
脑出血(ICH)是一种致死率和致残率都很高的破坏性疾病。可溶性环氧化物水解酶(SEH)是环二十碳三烯酸(EETs)信号转导途径中的关键酶。SEH抑制已被证明对多发性脑损伤具有神经保护作用。然而，其在脑出血后继发性损伤中的作用尚未完全阐明。在此，我们验证了1-Trifluoromethoxyphenyl-3(1-propionylpiperidin-4-yl)urea是一种有效的、高选择性的sEH抑制剂，可以抑制炎症和脑出血后的继发性损伤。成年雄性C57BL/6小鼠建立胶原酶诱导的脑出血模型。三七总皂甙可减轻血脑屏障损伤，抑制炎症反应，增加小胶质细胞M2极化，减少外周中性粒细胞的浸润。此外，TPPU还可减轻神经元损伤，促进功能恢复。结果提示，sEH可能是治疗脑出血的潜在靶点。
Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH.