Orta ve şiddetli kronik hipoksi sırasında sıçan akciğer dokusunda inflamatuvar yanıtta adenozinerjik sinyal yolunun hedeflenmesi

Year 2025, Volume: 50 Issue: 1, 22 - 37, 31.03.2025

Özge Göktepe , Kemal Erdem Başaran , Pınar Alişan Suna , Demet Bolat , Arzu Yay

https://doi.org/10.17826/cumj.1525573

Abstract

Amaç: Hipoksi, dokulardaki inflamatuar hastalıklardan sonra ortaya çıkar ve proinflamatuar yanıtların indüklenmesiyle ilişkilidir. Adenozin reseptörleri bu yanıtın başlatılması ve düzenlenmesinde kritik öneme sahiptir. Bu tür inflamatuar hastalıklarda haricen uygulanan adenozin reseptör agonistlerinin/antagonistlerinin etkinliği dikkat çekicidir. Bu çalışmada hipoksi, adenozin ve inflamasyon arasındaki ilişkinin yanı sıra adenozin agonist ve antagonistlerinin bu süreçteki rolünü araştırmayı amaçladık.
Gereç ve Yöntem: Bu amaçla, orta ve şiddetli olmak üzere iki farklı hipoksi modeli kullanıldı. Her iki model için toplam 80 erkek Sprague-Dawley sıçanı kullanılarak 4 alt grup tasarlandı: kontrol (CON), dimetil sülfoksit (DMSO), agonist (AGO; CGS-21680) ve antagonist (ANT; MSX-3). Sıçanlar 7 gün boyunca ince ayarlı normobarik hipoksi odalarında orta gruplarda %13 O2 ve ağır gruplarda %10 O2'ye maruz bırakıldı. 7. günün sonunda ventilasyon ölçümleri yapıldı ve hipoksi modeli doğrulandı. Deneysel aşamalardan sonra akciğer dokularından dondurulmuş kesitler alınarak immünofloresan boyama yöntemi ile A2AR, CD11c, COX2, NFKB ve VEGF antikor ekspresyonları değerlendirildi.
Bulgular: Bu çalışma, deneysel hipoksi modellerinde inflamatuar belirteçlerin ekspresyonunun arttığını gösterdi. Bulgulara göre, her iki modelde de agonist grubunda A2AR ve VEGF düzeyleri diğer gruplara göre daha yüksek iken, inflamasyon belirteçleri CD11c, NFKB ve COX2 düzeyleri anlamlı derecede düşüktü.
Sonuç: Enflamasyonu tedavi etmek için akciğer bozukluklarının tedavisinde yardımcı olabilecek çeşitli doğal ve sentetik ilaçlar mevcuttur. Araştırmacılar hala daha hızlı yanıt verebilecek yeni antiinflamatuar ilaçları araştırıyorlar. Bu bulgular hipoksi kaynaklı akciğer inflamasyonunda kullanılabilecek A2A agonistlerinin potansiyel faydasını vurgulamaktadır.

Keywords

Hipoksi, adenozin, adenozin agonist/antagonist, akciğer toksisitesi

Ethical Statement

All experimental procedures were approved by the Erciyes University Animal experiments local ethics committee at the meeting dated 05.05.2020, with decision number 20/081 before investigation.

Supporting Institution

With the project code of TKB-2020-10343, support was received from the Erciyes University Scientific Research Project unit.

Project Number

TKB-2020-10343

Targeting the adenosinergic signaling pathway in the inflammatory response in rat lung tissue during moderate and severe chronic hypoxia

Abstract

Purpose: Hypoxia occurs after inflammatory diseases in tissues and is associated with the induction of proinflammatory responses in addition to the breakdown of barriers. Adenosine receptors are critical in the initiation and regulation of this response. The effectiveness of externally applied adenosine receptor agonists/antagonists in such inflammatory diseases is noteworthy. In this study, we aimed to investigate the relationship between hypoxia, adenosine and inflammation, as well as the role of adenosine agonists and antagonists in this situation.
Materials and Methods: For this purpose, two different hypoxia models, moderate and severe, were used. Using a total of 80 male Sprague-Dawley rats for both models, 4 subgroups were designed: control (CON), dimethyl sulfoxide (DMSO), adenosine agonist (AGO; CGS-21680) and adenosine antagonist (ANT; MSX-3). Rats were exposed to moderate groups 13% O2 and severe groups 10% O2 in fine-tuned normobaric hypoxia chambers for 7 days. At the end of the 7th day, ventilation measurements were made and the hypoxia model was confirmed. A2AR, CD11c, COX2, NFKB and VEGF antibody expressions were evaluated by immunofluorescence staining method by taking frozen sections from the lung tissues after the experimental stages.
Results: This study showed that the expression of inflammation markers increased in experimental hypoxia models. According to the findings, while the levels of A2AR and VEGF were higher in the agonist group compared to the other groups in both models, the levels of inflammatory markers CD11c, NFKB and COX2 were significantly lower.
Conclusion: Various natural and synthetic drugs are available as treating the inflammation which can be helpful in treating lung disorders. Researchers are still searching for new anti-inflammatory drugs which can produced faster response. These findings highlight the potential benefit of A2A agonists, which can be used in hypoxia-induced lung inflammation.

Keywords

Hypoxia, Adenosine, Adenosine agonist/antagonist, Lung toxicity

Project Number

TKB-2020-10343

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