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1
Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage.罗氟司特减轻实验性蛛网膜下腔出血大鼠模型中的脑炎症。
Inflammation. 2017 Aug;40(4):1245-1253. doi: 10.1007/s10753-017-0567-8.
2
Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease.罗氟司特:一种用于治疗慢性阻塞性肺疾病的磷酸二酯酶 4 抑制剂的最新进展。
Br J Pharmacol. 2011 May;163(1):53-67. doi: 10.1111/j.1476-5381.2011.01218.x.
3
Effects of tadalafil (PDE5 inhibitor) and roflumilast (PDE4 inhibitor) on airway reactivity and markers of inflammation in ovalbumin-induced airway hyperresponsiveness in guinea pigs.他达拉非(磷酸二酯酶5抑制剂)和罗氟司特(磷酸二酯酶4抑制剂)对卵清蛋白诱导的豚鼠气道高反应性中气道反应性及炎症标志物的影响。
J Physiol Pharmacol. 2017 Oct;68(5):721-730.
4
The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.罗氟司特的临床前药理学——一种用于慢性阻塞性肺疾病的选择性、口服磷酸二酯酶 4 抑制剂。
Pulm Pharmacol Ther. 2010 Aug;23(4):235-56. doi: 10.1016/j.pupt.2010.03.011. Epub 2010 Apr 7.
5
Reduction of lung inflammation, oxidative stress and apoptosis by the PDE4 inhibitor roflumilast in experimental model of acute lung injury.磷酸二酯酶4抑制剂咯利普兰在急性肺损伤实验模型中对肺部炎症、氧化应激及细胞凋亡的抑制作用
Physiol Res. 2018 Dec 31;67(Suppl 4):S645-S654. doi: 10.33549/physiolres.934047.
6
Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition.罗氟司特通过 NLRP 介导的炎症反应抑制在幼年大鼠脑缺血/再灌注损伤中的神经保护作用。
Clin Exp Pharmacol Physiol. 2021 Aug;48(8):1103-1110. doi: 10.1111/1440-1681.13493. Epub 2021 May 10.
7
[Roflumilast: clinical review of a new option for the treatment of inflammation in COPD].[罗氟司特:慢性阻塞性肺疾病炎症治疗新选择的临床综述]
Arch Bronconeumol. 2010 Nov;46 Suppl 9:8-11. doi: 10.1016/S0300-2896(10)70047-8.
8
Pharmacological mechanism of roflumilast in the treatment of asthma-COPD overlap.罗氟司特治疗哮喘-慢性阻塞性肺疾病重叠综合征的药理机制
Drug Des Devel Ther. 2018 Aug 1;12:2371-2379. doi: 10.2147/DDDT.S165161. eCollection 2018.
9
Dose dependent effects of tadalafil and roflumilast on ovalbumin-induced airway hyperresponsiveness in guinea pigs.他达拉非和罗氟司特对卵清蛋白诱导的豚鼠气道高反应性的剂量依赖性影响。
Exp Lung Res. 2017 Nov-Dec;43(9-10):407-416. doi: 10.1080/01902148.2017.1386735. Epub 2017 Dec 8.
10
Alternatives to indicating roflumilast and the chronic obstructive pulmonary disease classification.罗氟司特的替代药物及慢性阻塞性肺疾病的分类
Arch Bronconeumol. 2012 Sep;48(9):343. doi: 10.1016/j.arbres.2012.02.010. Epub 2012 Apr 21.

引用本文的文献

1
The Lung-Brain Axis in Chronic Obstructive Pulmonary Disease-Associated Neurocognitive Dysfunction: Mechanistic Insights and Potential Therapeutic Options.慢性阻塞性肺疾病相关神经认知功能障碍中的肺-脑轴:机制洞察与潜在治疗选择
Int J Biol Sci. 2025 May 15;21(8):3461-3477. doi: 10.7150/ijbs.109261. eCollection 2025.
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PDE4 inhibitors: potential protective effects in inflammation and vascular diseases.磷酸二酯酶4抑制剂:在炎症和血管疾病中的潜在保护作用。
Front Pharmacol. 2024 Jun 10;15:1407871. doi: 10.3389/fphar.2024.1407871. eCollection 2024.
3
A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats.罗氟司特治疗成年雄性Wistar抑郁大鼠海马功能和结构变化的研究
PLoS One. 2024 Feb 5;19(2):e0296187. doi: 10.1371/journal.pone.0296187. eCollection 2024.
4
Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.两种磷酸二酯酶 4 抑制剂对脂多糖诱导的小鼠神经炎症的差异作用。
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5
Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury.释放脊髓修复:cAMP 特异性 PDE 抑制在减轻创伤性脊髓损伤后神经炎症和促进再生中的作用。
Int J Mol Sci. 2023 May 2;24(9):8135. doi: 10.3390/ijms24098135.
6
Blood-Brain Barrier Rescue by Roflumilast After Transient Global Cerebral Ischemia in Rats.罗氟司特对大鼠短暂性全脑缺血后血脑屏障的保护作用。
Neurotox Res. 2023 Aug;41(4):311-323. doi: 10.1007/s12640-023-00639-2. Epub 2023 Mar 16.
7
Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods.通过免疫组织化学和免疫荧光方法研究长期使用罗氟司特对大鼠睾丸组织的凋亡和自噬作用。
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TAT-HSP27 Peptide Improves Neurologic Deficits Reducing Apoptosis After Experimental Subarachnoid Hemorrhage.TAT-HSP27肽改善实验性蛛网膜下腔出血后的神经功能缺损并减少细胞凋亡。
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9
SERS-based immunoassay based on gold nanostars modified with 5,5'-dithiobis-2-nitrobenzoic acid for determination of glial fibrillary acidic protein.基于金纳米星修饰的 5,5'-二硫代双(2-硝基苯甲酸)的表面增强拉曼散射免疫分析用于测定神经胶质纤维酸性蛋白
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Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review.白细胞介素 6 与颅内动脉瘤性蛛网膜下腔出血:一项综述。
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本文引用的文献

1
Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats.咯利普兰通过环磷酸腺苷/环磷酸腺苷反应元件结合蛋白途径刺激大鼠缺血性中风后的血管生成并减轻神经元凋亡。
Exp Ther Med. 2016 Mar;11(3):1005-1010. doi: 10.3892/etm.2015.2958. Epub 2015 Dec 29.
2
The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses.磷酸二酯酶4(PDE4)抑制剂罗氟司特在非催吐剂量下可改善啮齿动物的记忆力。
Behav Brain Res. 2016 Apr 15;303:26-33. doi: 10.1016/j.bbr.2016.01.031. Epub 2016 Jan 18.
3
Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.纳米姜黄素通过抑制炎症反应和氧化应激增强对蛛网膜下腔出血诱导的血脑屏障破坏的治疗潜力。
Mol Neurobiol. 2017 Jan;54(1):1-14. doi: 10.1007/s12035-015-9635-y. Epub 2015 Dec 26.
4
Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.代谢型谷氨酸受体5(mGluR5)的激活减轻大鼠实验性蛛网膜下腔出血后早期脑损伤中的小胶质细胞激活和神经元凋亡。
Neurochem Res. 2015 Jun;40(6):1121-32. doi: 10.1007/s11064-015-1572-7. Epub 2015 Apr 7.
5
Cysteamine alleviates early brain injury via reducing oxidative stress and apoptosis in a rat experimental subarachnoid hemorrhage model.在大鼠实验性蛛网膜下腔出血模型中,半胱胺通过减轻氧化应激和细胞凋亡来缓解早期脑损伤。
Cell Mol Neurobiol. 2015 May;35(4):543-53. doi: 10.1007/s10571-014-0150-x. Epub 2014 Dec 20.
6
Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats.罗利普兰和罗氟司特,磷酸二酯酶-4 抑制剂,对高血压诱导的大鼠记忆功能缺陷的影响。
Eur J Pharmacol. 2015 Jan 5;746:138-47. doi: 10.1016/j.ejphar.2014.10.039. Epub 2014 Nov 6.
7
Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage.蛛网膜下腔出血后的炎症、血管痉挛和脑损伤。
Biomed Res Int. 2014;2014:384342. doi: 10.1155/2014/384342. Epub 2014 Jul 3.
8
Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis.磷酸二酯酶4和7抑制剂作为实验性自身免疫性脑脊髓炎治疗药物的比较评估
Br J Pharmacol. 2013 Oct;170(3):602-13. doi: 10.1111/bph.12308.
9
The phosphodiesterase-4 inhibitor rolipram protects from ischemic stroke in mice by reducing blood-brain-barrier damage, inflammation and thrombosis.磷酸二酯酶-4 抑制剂罗利普兰通过减少血脑屏障损伤、炎症和血栓形成来保护小鼠免受缺血性中风。
Exp Neurol. 2013 Sep;247:80-90. doi: 10.1016/j.expneurol.2013.03.026. Epub 2013 Apr 6.
10
The therapeutic profile of rolipram, PDE target and mechanism of action as a neuroprotectant following spinal cord injury.罗利普兰(rolipram)的治疗概况,PDE 靶点及作用机制,在脊髓损伤后作为神经保护剂。
PLoS One. 2012;7(9):e43634. doi: 10.1371/journal.pone.0043634. Epub 2012 Sep 19.

罗氟司特减轻实验性蛛网膜下腔出血大鼠模型中的脑炎症。

Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage.

作者信息

Wu Qingjian, Qi Lifeng, Li Hanxia, Mao Leilei, Yang Mingfeng, Xie Rongxia, Yang Xiaoyi, Wang Jian, Zhang Zongyong, Kong Jiming, Sun Baoliang

机构信息

Department of Neurology, Shandong University School of Medicine, Jinan, Shandong, 250012, China.

Department of Neurology, Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Affiliated Hospital of Taishan Medical University, Taian, Shandong, 271000, China.

出版信息

Inflammation. 2017 Aug;40(4):1245-1253. doi: 10.1007/s10753-017-0567-8.

DOI:10.1007/s10753-017-0567-8
PMID:28451841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6193485/
Abstract

Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti-inflammation drug for treatment of chronic obstructive pulmonary disease (COPD). This study investigates the effects of roflumilast on cerebral inflammation in the rat SAH model. Here, we show that subcutaneous administration of roflumilast (3 mg/kg) significantly improved the neurological deficits. Measurement of evans blue extravasation and brain water content revealed a significant reduction of blood-brain barrier permeability and brain edema. Importantly, roflumilast treatment remarkably decreased levels of IL-1β, IL-6, and TNF-α and the number of apoptotic neurons in the brain after SAH. These results indicate that roflumilast is effective in treating cerebral inflammation following SAH.

摘要

罗氟司特是一种磷酸二酯酶4(PDE4)的选择性抑制剂,已被美国食品药品监督管理局(FDA)批准作为一种抗炎药物用于治疗慢性阻塞性肺疾病(COPD)。本研究调查了罗氟司特对大鼠蛛网膜下腔出血(SAH)模型脑内炎症的影响。在此,我们发现皮下注射罗氟司特(3毫克/千克)可显著改善神经功能缺损。伊文思蓝外渗和脑含水量的测量结果显示血脑屏障通透性和脑水肿显著降低。重要的是,罗氟司特治疗显著降低了SAH后大脑中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平以及凋亡神经元的数量。这些结果表明罗氟司特对治疗SAH后的脑内炎症有效。