Department of Traditional Chinese Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
Sci Rep. 2022 Aug 18;12(1):14116. doi: 10.1038/s41598-022-17981-8.
Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.
急性放射性直肠炎（ARP）是盆腔放射治疗后最常见的并发症之一，其发生机制与炎症、血管生成等有关。本研究通过转录组测序、Western blot 和免疫组化等方法，观察地塞米松（DXM）联合庆大霉素（GM）灌肠对 ARP 模型小鼠的作用，并探讨其可能的作用机制。C57BL/6 小鼠随机分为 3 组：正常对照组、ARP 模型组、DXM+GM 灌肠治疗组。采用单次 6 MV X 射线 27 Gy 盆腔局部照射建立 ARP 模型小鼠。与正常组相比，ARP 组小鼠有 979 个基因共同上调，445 个基因共同下调。根据基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，我们首次发现，PI3K/AKT/NF-κB/VEGF 通路与 ARP 小鼠炎症诱导的血管生成关系最为密切。PI3K/AKT 通路导致 NF-κB 激活，从而促进 VEGF 和 Bcl-2 的转录。有趣的是，DXM+GM 灌肠治疗改善了 ARP 小鼠的症状和病理变化。DXM+GM 灌肠通过下调 NF-κB 并上调 AQP3 抑制炎症，通过下调 VEGF 和 AQP1 抑制血管生成，通过增加 Bax 并抑制 Bcl-2 诱导细胞凋亡。这些新的机制可能与下调 PI3K/AKT/NF-κB/VEGF 通路有关。
