Cytochrome P450 CYP2E1 Suppression Ameliorates Cerebral Ischemia Reperfusion Injury.
Cytochrome P450 CYP2E1 Suppression Ameliorates Cerebral Ischemia Reperfusion Injury.
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DOI：
10.3390/antiox10010052
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发表时间：
2021-01-05
期刊：
影响因子：
--
通讯作者：
Taheri S
中科院分区：
文献类型：
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作者：
Yu J;Zhu H;Kindy MS;Taheri S
尽管存在关于缺血/再灌注（I/R）后氧化标志物过度产生的有力证据，但氧化酶细胞色素P450- 2 E1（CYP 2 E1）促进I/R结局的机制尚不清楚。在本研究中，我们试图评估CYP 2 E1在I/R中的功能意义。对CYP 2 E1 KO小鼠和对照进行大脑中动脉闭塞（MCAo-90 min），随后再灌注24 h以诱导局灶性I/R损伤作为急性期模型。然后，进行组织学和化学分析，以研究CYP 2 E1在病变体积、氧化应激和炎症恶化中的作用。此外，通过测量20-羟基二十四烯酸（20-HETE）活性以及体内血脑屏障（BBB）转移速率，研究了CYP 2 E1对血脑屏障（BBB）完整性的作用。I/R后，与对照组相比，CYP 2 E1 KO小鼠表现出显著较低的病变体积和神经功能缺损（p < 0.005）。此外，CYP 2 E1（−/−）I/R组的活性氧（ROS）产生、细胞凋亡和神经退行性变显著降低（p < 0.001）。与野生型（WT）相比，CYP 2 E1（−/−）小鼠的BBB损伤显著降低（p < 0.001），而20-HETE产量增加了41%。此外，I/R后CYP 2 E1（−/−）小鼠的炎性细胞因子表达和活化小胶质细胞数量显著降低。CYP 2 E1抑制通过减少氧化应激和炎症来改善I/R损伤并保护BBB完整性。
Despite existing strong evidence on oxidative markers overproduction following ischemia/reperfusion (I/R), the mechanism by which oxidative enzyme Cytochrome P450-2E1 (CYP2E1) contributes to I/R outcomes is not clear. In this study, we sought to evaluate the functional significance of CYP2E1 in I/R. CYP2E1 KO mice and controls were subjected to middle cerebral artery occlusion (MCAo-90 min) followed by 24 h of reperfusion to induce focal I/R injury as an acute stage model. Then, histological and chemical analyses were conducted to investigate the role of CYP2E1 in lesion volume, oxidative stress, and inflammation exacerbation. Furthermore, the role of CYP2E1 on the blood-brain barrier (BBB) integrity was investigated by measuring 20-hydroxyecosatetraenoic acid (20-HETE) activity, as well as, in vivo BBB transfer rate. Following I/R, the CYP2E1 KO mice exhibited a significantly lower lesion volume, and neurological deficits compared to controls (p < 0.005). Moreover, reactive oxygen species (ROS) production, apoptosis, and neurodegeneration were significantly lower in the CYP2E1(−/−) I/R group (p < 0.001). The BBB damage was significantly lower in CYP2E1(−/−) mice compared to wild-type (WT) (p < 0.001), while 20-HETE production was increased by 41%. Besides, inflammatory cytokines expression and the number of activated microglia were significantly lower in CYP2E1(−/−) mice following I/R. CYP2E1 suppression ameliorates I/R injury and protects BBB integrity by reducing both oxidative stress and inflammation.
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CYP2E1在大脑中的药物代谢或生物活化中的作用。
影响因子：
--
作者：
García-Suástegui WA;Ramos-Chávez LA;Rubio-Osornio M;Calvillo-Velasco M;Atzin-Méndez JA;Guevara J;Silva-Adaya D
通讯作者：
Silva-Adaya D
高脂血症通过氧化应激、炎症和神经元凋亡加剧 MCAO/再灌注大鼠的脑损伤
影响因子：
2
作者：
Cao, Xiao-Lu;Du, Jing;Hu, Xia-Min
通讯作者：
Hu, Xia-Min
影响因子：
3.9
作者：
Cheung, C;Yu, AM;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.
影响因子：
11.4
作者：
Cederbaum, Arthur I.
通讯作者：
Cederbaum, Arthur I.