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咖啡因通过腺苷 A2A 受体/cAMP/PKA/Src/ERK1/2/p38MAPK 通路减少氧化应激，从而预防高氧诱导的肺损伤。

Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway.

机构信息

Department of Paediatrics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, People's Republic of China.

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Redox Rep. 2022 Dec;27(1):270-278. doi: 10.1080/13510002.2022.2143114.

DOI:10.1080/13510002.2022.2143114
PMID:36357965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9662006/
Abstract

Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro. Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 μM caffeine), antagonist (5 μM ZM241385), agonist (5 μM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II. Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine. Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. Caffeine and A2AR may serve as a promising therapeutic target for BPD in prematurity.

摘要

咖啡因已被证明可降低支气管肺发育不良（BPD）的发生率。为了在体外基于高氧的 BPD 细胞模型中研究咖啡因的保护机制。分离并随机将 II 型肺泡上皮细胞（AECs II）分为 6 组：正常组、高氧组、咖啡因组（50μM 咖啡因）、拮抗剂组（5μM ZM241385）、激动剂组（5μM CGS21680）和 DMSO 组。在 AECs II 中转染腺苷 A2A 受体（A2AR）的 siRNA。咖啡因单独或与腺苷 A2A 受体（A2AR）拮抗剂联合使用可抑制细胞凋亡、促进增殖并减轻氧化应激（OS）。与高氧组相比，咖啡因和拮抗剂组的环磷酸腺苷（cAMP）、蛋白激酶 A（PKA）mRNA、A2AR mRNA 以及 A2AR、磷酸化Src、磷酸化 ERK1/2、磷酸化 P38 和裂解 caspase-3 的蛋白水平均降低。然而，A2AR 激动剂减弱了咖啡因的上述作用。A2AR 敲低的结果与咖啡因相似。咖啡因通过抑制 A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK 信号通路，可减少高氧诱导的 AECs II 损伤中的细胞凋亡、促进增殖并减轻 OS。咖啡因和 A2AR 可能是早产儿 BPD 的有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/aebf3e6d3967/YRER_A_2143114_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/db6e49333e2f/YRER_A_2143114_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/152ada489320/YRER_A_2143114_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/7c2853636f7a/YRER_A_2143114_F0003_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/fa63e7b6e389/YRER_A_2143114_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/50b53c0f2857/YRER_A_2143114_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/aebf3e6d3967/YRER_A_2143114_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/db6e49333e2f/YRER_A_2143114_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/152ada489320/YRER_A_2143114_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/7c2853636f7a/YRER_A_2143114_F0003_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/fa63e7b6e389/YRER_A_2143114_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/50b53c0f2857/YRER_A_2143114_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbd/9662006/aebf3e6d3967/YRER_A_2143114_F0006_OC.jpg

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