T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin-1-Like Protein Pathway.
T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin-1-Like Protein Pathway.
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T0901317是肝X受体的激动剂T0901317，可通过肝脏X受体/干扰素调节因子/p53上调调节剂/p53的调节剂的调节剂/p53在大鼠的蛛网膜下腔出血后早期脑损伤减弱神经元凋亡。
DOI：
10.1155/2021/8849131
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发表时间：
2021
影响因子：
--
通讯作者：
Shi H
中科院分区：
文献类型：
--
作者：
Dai J;Xu S;Okada T;Liu Y;Zuo G;Tang J;Zhang JH;Shi H
采用穿孔法建立SD大鼠蛛网膜下腔出血（SAH）模型。SAH后1小时腹膜内注射T0901317。将GSK 2033（LXR的抑制剂）和干扰素调节因子（IRF-1）CRISPR活化脑室内注射以评估潜在的信号传导途径。Western blot和免疫荧光染色检测SAH严重程度、神经行为学检查和细胞凋亡。 与Sham组相比，SAH+溶剂组LXR-α和IRF-1的表达增加，并在SAH后24 h达到峰值，而LXR-β则不受影响。SAH后T0901317治疗在短期和长期中减弱神经元损伤，并减少神经元凋亡，IRF-1，P53上调凋亡调节因子（CD 4A），发动蛋白-1样蛋白（Drp 1），Bcl-2相关X蛋白（Bax）和裂解的caspase-3的表达，并在建模后24 h增加B细胞淋巴瘤2（Bcl-2）。GSK 2033抑制LXR并逆转T0901317的神经保护作用。IRF-1 CRISPR激活上调了IRF-1的表达，并消除了T0901317的治疗作用。 T0901317通过LXRs/IRF-1/DRPA/Drp 1通路减轻SAH大鼠神经元凋亡。
Subarachnoid hemorrhage (SAH) models of Sprague-Dawley rats were established with perforation method. T0901317 was injected intraperitoneally 1-hour post-SAH. GSK2033, an inhibitor of LXRs, and interferon regulatory factor (IRF-1) CRISPR activation were injected intracerebroventricularly to evaluate potential signaling pathway. The severity of SAH, neurobehavior test in both short- and long-term and apoptosis was measured with Western blot and immunofluorescence staining. Expression of LXR-α and IRF-1 increased and peaked at 24 h post-SAH, while LXR-β remained unaffected in SAH+vehicle group compared with Sham group. Post-SAH T0901317 treatment attenuated neuronal impairments in both short- and long-term and decreased neuronal apoptosis, the expression of IRF-1, P53 upregulated modulator of apoptosis (PUMA), dynamin-1-like protein (Drp1), Bcl-2-associated X protein (Bax) and cleaved caspase-3, and increasing B-cell lymphoma 2 (Bcl-2) at 24 h from modeling. GSK2033 inhibited LXRs and reversed T0901317's neuroprotective effects. IRF-1 CRISPR activation upregulated the expression of IRF-1 and abolished the treatment effects of T0901317. T0901317 attenuated neuronal apoptosis via LXRs/IRF-1/PUMA/Drp1 pathway in SAH rats.
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影响因子：
4.6
作者：
Hichor M;Sundaram VK;Eid SA;Abdel-Rassoul R;Petit PX;Borderie D;Bastin J;Eid AA;Manuel M;Grenier J;Massaad C
通讯作者：
Massaad C
影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
48
作者：
Nieuwkamp, Dennis J.;Setz, Larissa E.;Rinkel, Gabriel E.
通讯作者：
Rinkel, Gabriel E.
影响因子：
8.3
作者：
Cui X;Chopp M;Zacharek A;Cui Y;Roberts C;Chen J
通讯作者：
Chen J
DOI：
10.1073/pnas.0711599105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Kim, Hyun-Jin;Fan, Xiaotang;Gustafsson, Jan-Ake
通讯作者：
Gustafsson, Jan-Ake