Argon reduces microglial activation and inflammatory cytokine expression in retinal ischemia/reperfusion injury.
Argon reduces microglial activation and inflammatory cytokine expression in retinal ischemia/reperfusion injury.
复制标题
氩气可减轻视网膜缺血/再灌注损伤中的小胶质细胞活化及炎性细胞因子表达。
DOI：
10.4103/1673-5374.290098
复制
发表时间：
2021-01
影响因子：
6.1
通讯作者：
Ulbrich F
中科院分区：
文献类型：
--
作者：
Goebel U;Scheid S;Spassov S;Schallner N;Wollborn J;Buerkle H;Ulbrich F
我们之前发现氩的神经保护作用部分是通过抑制toll样受体（TLR） 2和4来实现的。下游转录因子信号转导和转录激活因子3 （STAT3）和核因子κB （NF-κB）也受到氩气的影响，并可能发挥神经保护作用。研究还表明，氩气治疗可以减轻脑损伤，减少过度的小胶质细胞激活，从而减轻脑炎症。尽管进行了深入的研究，但进一步的确切机制仍不清楚。在这项研究中，人神经母细胞瘤细胞在体外用鱼藤酮损伤4小时（模拟脑缺血和再灌注损伤），然后用氩气（75%）处理2小时。在单独的体内实验中，通过增加眼压1小时诱导大鼠视网膜缺血再灌注损伤。再灌注后，吸入氩气2小时。氩气降低了参与神经元损伤调控的转录因子信号转导和转录激活因子3、核因子κ B、激活蛋白1、核因子红系2相关因子2的结合。流式细胞术分析表明，氩气对Fas配体有下调作用。部分转录因子受toll样受体调控；因此，它们的作用可以被TLR2和TLR4抑制剂氧化磷脂1-棕榈酰-2-花生四烯酰基- rn -甘油-3-磷酸胆碱（OxPAPC）至少部分消除。氩气治疗可降低视网膜缺血再灌注损伤后小胶质细胞的活化。随后的定量聚合酶链反应分析显示，促炎细胞因子白介素（IL-1α）、IL-1β、IL-6、肿瘤坏死因子α和诱导型一氧化氮合酶均减少。我们的研究结果表明，氩气通过抑制对小胶质细胞激活至关重要的转录因子，降低了缺血/再灌注损伤后视网膜神经元的炎症程度。氩气没有已知的副作用或麻醉特性；因此，使用这种惰性气体治疗视网膜缺血/再灌注损伤中神经元损伤的患者似乎是理想的。动物实验于2012年10月19日获得弗莱堡大学动物护理委员会批准（批准号35-9185.81/G14-122）。
We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors (TLR) 2 and 4. The downstream transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) are also affected by argon and may play a role in neuroprotection. It also has been demonstrated that argon treatment could mitigate brain damage, reduce excessive microglial activation, and subsequently attenuate brain inflammation. Despite intensive research, the further exact mechanism remains unclear. In this study, human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours (to mimic cerebral ischemia and reperfusion damage), followed by a 2-hour post-conditioning with argon (75%). In a separate in vivo experiment, retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour. Upon reperfusion, argon was administered by inhalation for 2 hours. Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3, nuclear factor kappa B, activator protein 1, and nuclear factor erythroid 2-related factor 2, which are involved in regulation of neuronal damage. Flow cytometry analysis showed that argon downregulated the Fas ligand. Some transcription factors were regulated by toll-like receptors; therefore, their effects could be eliminated, at least in part, by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC). Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury. Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin (IL-1α), IL-1β, IL-6, tumor necrosis factor α, and inducible nitric oxide synthase. Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation. Argon has no known side effects or narcotic properties; therefore, therapeutic use of this noble gas appears ideal for treatment of patients with neuronal damage in retinal ischemia/reperfusion injury. The animal experiments were approved by the Commission for Animal Care of the University of Freiburg (approval No. 35-9185.81/G14-122) on October 19, 2012.
登录
查看更多内容
影响因子：
15.1
作者：
Liu, Jingjin;Nolte, Kay;Coburn, Mark
通讯作者：
Coburn, Mark
通过增强 GABA 释放来降低 c-Jun N 末端激酶 3 (JNK3) 的激活，从而对乙醇进行神经保护，防止缺血/再灌注引起的脑损伤
影响因子：
3.3
作者：
Qi, S. -H.;Liu, Y.;Zhang, G. -Y.
通讯作者：
Zhang, G. -Y.
影响因子：
5
作者：
Fahlenkamp, Astrid V.;Rossaint, Rolf;Coburn, Mark
通讯作者：
Coburn, Mark
影响因子：
4.7
作者：
Przanowski, Piotr;Dabrowski, Michal;Ellert-Miklaszewska, Aleksandra;Kloss, Michal;Mieczkowski, Jakub;Kaza, Beata;Ronowicz, Anna;Hu, Feng;Piotrowski, Arkadiusz;Kettenmann, Helmut;Komorowski, Jan;Kaminska, Bozena
通讯作者：
Kaminska, Bozena
影响因子：
3.4
作者：
Planas, AM;Soriano, MA;Ferrer, I
通讯作者：
Ferrer, I