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低氧后处理活化腺苷A2a受体抑制皮瓣微血管内皮细胞凋亡

Hypoxic Postconditioning Attenuates Apoptosis Via Activation of Adenosine A2a Receptors on Human Dermal Microvascular Endothelial Cells
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摘要 目的:本研究致力于探求腺苷A2a在低氧后处理抗凋亡中的作用。方法:从人上睑皮肤组织中分离培养原代人皮肤微血管内皮细胞,经6h低氧培养后,置于正常氧环境培养12h;或者经过5min常氧/5min低氧,3次循环,即低氧后处理,之后再常氧培养11.5h。结果:细胞凋亡比例和细胞凋亡相关蛋白(Bax/Bcl-2和caspase-3)表达量增高,均证明低氧/复氧可引起严重的损伤(P〈0.05)。低氧后处理和选择性A2a受体激动剂——CGS-21680均可降低前两者(P〈0.05)。同时,低氧后处理和CGS-21680均明显活化了腺苷A2a受体(P〈0.05)。数据分析显示,凋亡的增加量与A2a受体蛋白的表达增加量呈显著负相关(γ^2=0.8177,P〈0.0001)。结论:低氧后处理通过活化皮肤微血管内皮细胞表面的A2a受体发挥抑制凋亡的作用。 Objective We aimed to identify the role of adenosine Aza receptor in the anti-apoptotic effects of HPC. Methods The HDMECs were isolated from human upper eyelid tissue. After 6 h of hypoxia, the HDMECs were either abruptly reperfused with preoxygenized culture medium for 12 h or postconditioned by three cycles of 5 min of brief reoxygenation and 5 min of re-hypoxia followed by 11.5 h of abrupt reoxygenation. Results Adenosine A2a receptors were detected in the cytoplasm of HDMECs. Hypoxia/reoxygenation (H/R) resulted in severe injury in HDMECs as evidenced by an increase in apoptosis percentage and an increase in expressions of apoptosis-related proteins (the ratio of Bax/Bcl-2 and caspase-3), which can be significantly attenuated by HPC treatment or exposure to CGS-21680, a selective adenosine A2a receptor agonist (all P values 〈0.05). Meanwhile, HPC treatment or CGS-21680 significantly activated A2a receptors compared with the H/ R group (P〈0.05 vs. P 〈0.05, respectively). Statistical analysis showed that the increase of cell apoptosis closely correlated inversely with the increase of relative protein level of adenosine A2a receptors (γ^2=0.8177,P〈0.0001). Conclusion Hypoxic postconditioning protects against apoptosis induced by reoxygenation via activation of adenosine A/a receptors on HDMECs.
出处 《中国美容医学》 CAS 2017年第3期70-74,共5页 Chinese Journal of Aesthetic Medicine
基金 两项国家自然科学基金资助(Nos.81272130,81571922)
关键词 游离皮瓣 人皮肤微血管内皮细胞 凋亡 低氧后处理 腺苷A2A受体 free flap human dermal microvascular endothelial cells apoptosis hypoxic postconditioning adenosine A2areceptors
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