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瑞格列替尼通过衰老模拟剂对血管缺血/再灌注损伤后内皮功能的性别特异性保护。

Sex-Specific Protection of Endothelial Function after Vascular Ischemia/Reperfusion Injury by the Senomorphic Agent Ruxolitinib.

机构信息

Department of Cardiac Surgery, University Hospital Halle, 06120 Halle, Germany.

Department of Cardiac Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11727. doi: 10.3390/ijms241411727.

DOI:10.3390/ijms241411727
PMID:37511486
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10381013/
Abstract

Ischemia/reperfusion (I/R)-induced endothelial dysfunction occurs in various cardiovascular disorders. I/R injury is partially driven by the release of cytokines. Known for its use in senotherapy, the JAK inhibitor ruxolitinib is able to block the release of cytokines. We investigated the effect of ruxolitinib on the cytokine release and endothelial-dependent vasorelaxation in an in vitro model of I/R. Aortic segments of C57BL/6J mice (N = 12/group) were divided into three groups: control, in vitro I/R (I/R group), and in vitro I/R with ruxolitinib during ischemic incubation (I/R+Ruxo group). We determined cytokine expression. In organ bath chambers, we investigated the maximal endothelial-dependent relaxation to acetylcholine (RACh) and maximal endothelial-independent relaxation to sodium-nitroprusside (RSNP). RACh was decreased in I/R compared to the control (83.6 ± 2.4 vs. 48.6 ± 3.4%; < 0.05) and I/R+Ruxo (74.4 ± 2.6 vs. 48.6 ± 3.4%; < 0.05). RSNP was comparable between all groups. IL-10 was detectable only in I/R+Ruxo. CXCL5, CCL2, CCL3, CCL8, CCL11, ICAM-1, IL-1α, IL-7, TNF-α, and G-CSF were decreased or not detectable in I/R+Ruxo. In I/R+Ruxo, ICAM-1 was reduced in rings only from male mice. Treatment of the aorta from mice during in vitro ischemia with the senomorphic agent ruxolitinib reduces cytokine release and protects the endothelium from I/R-mediated dysfunction.

摘要

缺血/再灌注（I/R）诱导的内皮功能障碍发生在各种心血管疾病中。I/R 损伤部分是由细胞因子的释放驱动的。作为衰老治疗的已知药物，JAK 抑制剂芦可替尼能够阻止细胞因子的释放。我们研究了芦可替尼对体外 I/R 模型中细胞因子释放和内皮依赖性血管舒张的影响。C57BL/6J 小鼠的主动脉段（N=12/组）分为三组：对照组、体外 I/R 组（I/R 组）和体外 I/R 期间缺血孵育时的芦可替尼组（I/R+Ruxo 组）。我们测定了细胞因子的表达。在器官浴槽室中，我们研究了乙酰胆碱（RACh）的最大内皮依赖性松弛和硝普钠（RSNP）的最大内皮非依赖性松弛。与对照组相比，I/R 组的 RACh 降低（83.6±2.4%比 48.6±3.4%； <0.05），I/R+Ruxo 组也降低（74.4±2.6%比 48.6±3.4%； <0.05）。所有组之间的 RSNP 相似。仅在 I/R+Ruxo 组中可检测到 IL-10。CXCL5、CCL2、CCL3、CCL8、CCL11、ICAM-1、IL-1α、IL-7、TNF-α和 G-CSF 在 I/R+Ruxo 组中减少或无法检测到。在 I/R+Ruxo 组中，只有雄性小鼠的环中 ICAM-1 减少。在体外缺血期间用衰老药物芦可替尼处理来自小鼠的主动脉可减少细胞因子的释放，并保护内皮免受 I/R 介导的功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a13/10381013/17a1c5fe89df/ijms-24-11727-g009.jpg
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本文引用的文献

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Pharmaceutics. 2022 May 6;14(5):1001. doi: 10.3390/pharmaceutics14051001.
3
Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis.关注性别：类风湿关节炎管理中我们需要了解的内容。
重定向药物用于衰老治疗：女性合成激素的潜在衰老改善作用。
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4
The Pro-Oncogenic Protein IF Promotes Proliferation of Anoxic Cancer Cells during Re-Oxygenation.促癌蛋白 IF 在再复氧时促进缺氧癌细胞的增殖。
Int J Mol Sci. 2023 Sep 27;24(19):14624. doi: 10.3390/ijms241914624.
5
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J Clin Med. 2023 Aug 22;12(17):5454. doi: 10.3390/jcm12175454.
J Pers Med. 2022 Mar 20;12(3):499. doi: 10.3390/jpm12030499.
4
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5
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Free Radic Biol Med. 2021 Mar;165:265-281. doi: 10.1016/j.freeradbiomed.2021.01.040. Epub 2021 Jan 23.