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探索碘化物和硫化氢作为活性氧清除剂以延缓 MHC 定义的血管化复合异体移植物中的急性排斥反应。

Exploring Iodide and Hydrogen Sulfide as ROS Scavengers to Delay Acute Rejection in MHC-Defined Vascularized Composite Allografts.

作者信息

Tratnig-Frankl Philipp, Andrews Alec R, Berkane Yanis, Guinier Claire, Goutard Marion, Lupon Elise, Lancia Hyshem H, Morrison Michael L, Roth Mark B, Randolph Mark A, Cetrulo Curtis L, Lellouch Alexandre G

机构信息

Division of Plastic, Reconstructive and Aesthetic Surgery, Vienna General Hospital, Medical University of Vienna, 1090 Vienna, Austria.

Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Antioxidants (Basel). 2024 Apr 26;13(5):531. doi: 10.3390/antiox13050531.

Abstract

Vascularized composite allografts (VCA) face ischemic challenges due to their limited availability. Reperfusion following ischemia triggers oxidative stress and immune reactions, and scavenger molecules could mitigate ischemia-reperfusion injuries and, therefore, immune rejection. We compared two scavengers in a myocutaneous flap VCA model. In total, 18 myocutaneous flap transplants were performed in Major histocompatibility complex (MHC)-defined miniature swine. In the MATCH group (n = 9), donors and recipients had minor antigen mismatch, while the animals were fully mismatched in the MISMATCH group (n = 9). Grafts were pretreated with saline, sodium iodide (NaI), or hydrogen sulfide (HS), stored at 4 °C for 3 h, and then transplanted. Flaps were monitored until clinical rejection without immunosuppression. In the MATCH group, flap survival did not significantly differ between the saline and hydrogen sulfide treatments ( = 0.483) but was reduced with the sodium iodide treatment ( = 0.007). In the MISMATCH group, survival was similar between the saline and hydrogen sulfide treatments ( = 0.483) but decreased with the sodium iodide treatment ( = 0.007). Rhabdomyolysis markers showed lower but non-significant levels in the experimental subgroups for both the MATCH and MISMATCH animals. This study provides insightful data for the field of antioxidant-based approaches in VCA and transplantation.

摘要

血管化复合组织异体移植(VCA)由于其可获得性有限而面临缺血挑战。缺血后的再灌注会引发氧化应激和免疫反应,而清除剂分子可以减轻缺血再灌注损伤,从而减轻免疫排斥反应。我们在肌皮瓣VCA模型中比较了两种清除剂。总共在主要组织相容性复合体(MHC)定义的小型猪中进行了18例肌皮瓣移植。在匹配组(n = 9)中,供体和受体的次要抗原不匹配,而在不匹配组(n = 9)中动物完全不匹配。移植物用盐水、碘化钠(NaI)或硫化氢(HS)预处理,在4℃下储存3小时,然后进行移植。监测皮瓣直至在没有免疫抑制的情况下发生临床排斥反应。在匹配组中,盐水和硫化氢处理之间的皮瓣存活率没有显著差异(P = 0.483),但碘化钠处理使其降低(P = 0.007)。在不匹配组中,盐水和硫化氢处理之间的存活率相似(P = 0.483),但碘化钠处理使其降低(P = 0.007)。横纹肌溶解标志物在匹配和不匹配动物的实验亚组中均显示出较低但不显著的水平。这项研究为VCA和移植领域基于抗氧化剂的方法提供了有见地的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1202/11118872/df56945e6c5f/antioxidants-13-00531-g001.jpg

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