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聚乳酸-羟基乙酸共聚物-聚乙二醇/全氟辛烷乳液的高效再氧合:ROS 和 HIF-1α 之间的反馈关系。

High-performance reoxygenation from PLGA-PEG/PFOB emulsions: a feedback relationship between ROS and HIF-1α.

机构信息

School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

出版信息

Int J Nanomedicine. 2018 May 22;13:3027-3038. doi: 10.2147/IJN.S155509. eCollection 2018.

DOI:10.2147/IJN.S155509
PMID:29861634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5968788/
Abstract

BACKGROUND

Hypoxemia is one of the most common pathological processes in various clinical diseases.

METHODS

A novel emulsion of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide has been developed to improve arterial hypoxemia through pulmonary drug delivery. Hypoxia-reoxygenation experiment was used to investigate the ability of the emulsion to supply oxygen and the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion.

RESULTS

It has been demonstrated that an apparent increase has been detected in the cytotoxicity test of the emulsion, indicating its lower cell toxicity. A hypoxia-reoxygenation experiment uncovered the fact that notable cell growth was observed after reoxygenation with poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide emulsion because of the ability of the emulsion to supply oxygen adequately and reasonably. Moreover, the level of intracellular reactive oxygen species was significantly enhanced during hypoxia, which further influenced the concentration and activity of hypoxia-inducible factor-1α (HIF-1α). Furthermore, the upregulated expression of HIF-1α during hypoxia has verified that certain emulsions can increase HIF-1α content and relieve hypoxia, which further indicates HIF-1α plays an essential role in improving cell viability. Afterwards, the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion and the result shows considerable improvement of lung ventilation of rabbits.

CONCLUSION

We recommend that the feedback relationship between reactive oxygen species and HIF-1 plays an essential role in improving cell viability. It is anticipated that the emulsion will be applied in the field of alleviating hypoxemia.

摘要

背景

低氧血症是各种临床疾病中最常见的病理过程之一。

方法

开发了一种新型的聚(乳酸-共-乙醇酸)-聚(乙二醇)/全氟辛基溴乳液,通过肺部药物输送来改善动脉低氧血症。采用缺氧-复氧实验研究乳液供氧能力,建立生理盐水灌洗急性肺损伤模型评价乳液供氧。

结果

细胞毒性试验表明,乳液的细胞毒性明显降低,表明其细胞毒性较低。缺氧-复氧实验表明,聚(乳酸-共-乙醇酸)-聚(乙二醇)/全氟辛基溴乳液具有合理充足的供氧能力,复氧后细胞生长明显。此外,缺氧时细胞内活性氧水平显著升高,进一步影响缺氧诱导因子-1α(HIF-1α)的浓度和活性。此外,缺氧时 HIF-1α 的上调表达证实了某些乳液可以增加 HIF-1α 的含量并缓解缺氧,进一步表明 HIF-1α 在提高细胞活力方面起着重要作用。随后,建立了生理盐水灌洗急性肺损伤模型来评价乳液的供氧情况,结果表明兔子的肺通气有了相当大的改善。

结论

我们认为活性氧和 HIF-1 之间的反馈关系在提高细胞活力中起着重要作用。预计该乳液将在缓解低氧血症领域得到应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/8bfa46c8330d/ijn-13-3027Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/9e8de9de3f12/ijn-13-3027Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/6a625b3c58bb/ijn-13-3027Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/49716b205898/ijn-13-3027Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/68d170945ddf/ijn-13-3027Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/62c57bf4d7dc/ijn-13-3027Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/bbb4a5324501/ijn-13-3027Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/8bfa46c8330d/ijn-13-3027Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/9e8de9de3f12/ijn-13-3027Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/3211fb44d145/ijn-13-3027Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/b503acc18cb0/ijn-13-3027Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/6a625b3c58bb/ijn-13-3027Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/49716b205898/ijn-13-3027Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/68d170945ddf/ijn-13-3027Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/62c57bf4d7dc/ijn-13-3027Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/bbb4a5324501/ijn-13-3027Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99d8/5968788/8bfa46c8330d/ijn-13-3027Fig9.jpg

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