Long Non-coding RNA H19 Promotes NLRP3-Mediated Pyroptosis After Subarachnoid Hemorrhage in Rats
Long Non-coding RNA H19 Promotes NLRP3-Mediated Pyroptosis After Subarachnoid Hemorrhage in Rats
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长链非编码RNA H19促进大鼠蛛网膜下腔出血后NLRP 3介导的细胞凋亡
DOI：
10.1007/s12975-022-01104-6
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发表时间：
2022-11
影响因子：
6.9
通讯作者：
Yibo Liu;Yujie Luo;Anke Zhang;Zefeng Wang;Xiaoyu Wang;Qian Yu;Zeyu Zhang;Zhoule Zhu;
中科院分区：
文献类型：
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作者：
Yibo Liu;Yujie Luo;Anke Zhang;Zefeng Wang;Xiaoyu Wang;Qian Yu;Zeyu Zhang;Zhoule Zhu;
据报道，NLRP 3炎性小体是蛛网膜下腔出血（SAH）后早期脑损伤（EBI）期间炎症反应的重要介质。最近的研究表明，NLRP 3炎性小体介导的焦亡和长链非编码RNA（lncRNA）H19可以参与炎症反应。然而，lncRNA H19在SAH后EBI期间NLRP 3炎性小体介导的焦亡中的作用和功能尚不清楚，需要进一步阐明。NLRP 3炎性体蛋白在SAH诱发EBI患者脑脊液中表达明显升高，并与SAH严重程度呈正相关。在SAH后24 h，NLRP 3和H19表达均达到高峰。然而，敲低H19显著降低大鼠SAH后24 h NLRP 3炎性体蛋白的表达，并改善EBI，表现出改善的神经行为缺陷、脑水肿和神经元损伤。此外，敲低H19下调SAH大鼠小胶质细胞Gasdermin D（GSDMD）的表达。类似地，H19的敲低也减轻了原代小胶质细胞中OxyHb诱导的焦亡和NLRP 3介导的炎性小体活化。最后，H19竞争性地吸收了rno-miR-138- 5 p，然后在SAH后炎症反应中上调NLRP 3表达。lncRNA H19在大鼠SAH后EBI中通过充当rno-miR-138- 5 p海绵促进NLRP 3介导的细胞凋亡，这可能为SAH后炎症调节提供潜在的治疗靶点。
NLRP3 inflammasomes have been reported to be an essential mediator in the inflammatory response during early brain injury (EBI) following subarachnoid hemorrhage (SAH). Recent studies have indicated that NLRP3 inflammasome-mediated pyroptosis and long non-coding RNA (lncRNA) H19 can participate in the inflammatory response. However, the roles and functions of lncRNA H19 in NLRP3 inflammasome-mediated pyroptosis during EBI after SAH are unknown and need to be further elucidated. NLRP3 inflammasome proteins were significantly elevated in CSF of human with SAH induced EBI and presented a positive correlation with severity. In ipsilateral hemisphere cortex of rats, these NLRP3 inflammasome proteins were also increased and accompanied with upregulation of H19, and both of NLRP3 and H19 were peaked at 24 h after SAH. However, knockdown of H19 markedly decreased the expression of NLRP3 inflammasome proteins at 24 h after SAH in rats and also ameliorated EBI, showing improved neurobehavioral deficits, cerebral edema, and neuronal injury. Moreover, knocking down of H19 downregulated the expression of Gasdermin D (GSDMD) in microglia in SAH rats. Similarly, knockdown of H19 also alleviated OxyHb-induced pyroptosis and NLRP3-mediated inflammasomes activation in primary microglia. Lastly, H19 competitively sponged with rno-miR-138-5p and then upregulated NLRP3 expression in the post-SAH inflammatory response. lncRNA H19 promotes NLRP3-mediated pyroptosis by functioning as rno-miR-138-5p sponge in rats during EBI after SAH, which might provide a potential therapeutic target for post-SAH inflammation regulation.