Experimental Surgery Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga #15 Belisario Dominguez, Mexico City.
Physiol Res. 2024 Nov 19;73(5):809-817. doi: 10.33549/physiolres.935385.
Primary graft failure occurs 15 to 30 % of the time after transplantation. Although there have been improvements in preserving the lungs in good condition, there have not been studies on the regulation of transcription factors.
We carried out an experimental study involving lung transplantation to indirectly evaluate reactive oxygen species (ROS) production and VEGF expression by competitive blockade of HIF-1alpha with chetomin. There were 5 groups: Group-1: Lung blocks were perfused with 0.9 % SSF, immediately harvested, and preserved. Group-2 (I-T): Immediate transplantation and then reperfusion for 1 h. Group-3 (I-R): Lung blocks were harvested and preserved in LPD solution for 6 h and reperfused for 1 h. Group-4 (DMSO): Lung blocks were treated for 4 h with DMSO, preserved for 6 h and transplanted to a receptor treated with DMSO. Group-5 (chetomin): Lung blocks were treated for 4 h with chetomin, preserved for 6 h and transplanted to a receptor treated with chetomin. ROS, mRNA, and protein levels of HIF-1alpha and EG-VEGF were determined.
The DMSO and chetomin groups had significantly lower ROS levels. Compared with those in the I-R group, the chetomin group exhibited the lowest level of HIF-1alpha.
Addition of chetomin to the donor and the receptor results in a significant reduction in HIF-1A, VEGF and ROS.
移植后 15-30%的时间会发生原发性移植物失功。尽管在保持肺良好状态方面已有改进,但对于转录因子的调节尚未进行研究。
我们进行了一项涉及肺移植的实验研究,通过使用 chetomin 竞争性阻断 HIF-1alpha 来间接评估活性氧(ROS)的产生和 VEGF 的表达。共分为 5 组:组 1:肺块用 0.9%SSF 灌注,立即收获并保存。组 2(I-T):立即移植,然后再灌注 1 小时。组 3(I-R):肺块收获后用 LPD 溶液保存 6 小时,然后再灌注 1 小时。组 4(DMSO):肺块用 DMSO 处理 4 小时,保存 6 小时并移植到用 DMSO 处理的受体。组 5(chetomin):肺块用 chetomin 处理 4 小时,保存 6 小时并移植到用 chetomin 处理的受体。测定 ROS、HIF-1alpha 和 EG-VEGF 的 mRNA 和蛋白水平。
DMSO 和 chetomin 组的 ROS 水平显著降低。与 I-R 组相比,chetomin 组的 HIF-1alpha 水平最低。
在供体和受体中添加 chetomin 可显著降低 HIF-1A、VEGF 和 ROS。