Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.
Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.
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多孔Se@SiO2纳米球包被导管通过抑制活性氧物种- nf -κB通路调节巨噬细胞极化，促进前列腺尿道创面愈合。
DOI：
10.1016/j.actbio.2019.02.006
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发表时间：
2019-04
影响因子：
9.7
通讯作者：
Bo-Yu Yang;Guoying Deng;Ruizhe Zhao;Chen-yun Dai;Chenyi Jiang;Xing-Jie Wang;Y. Jing;Xi-Jian Liu
中科院分区：
文献类型：
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作者：
Bo-Yu Yang;Guoying Deng;Ruizhe Zhao;Chen-yun Dai;Chenyi Jiang;Xing-Jie Wang;Y. Jing;Xi-Jian Liu
良性前列腺增生（BPH）患者在手术后会出现并发症。我们研究了多孔Se@SiO2nanospheres在经尿道前列腺切除术（TURP）后前列腺尿道伤口愈合中的氧化应激清除作用。建立TURP模型后，将Beagle犬随机分为两组。评估伤口恢复和氧化应激水平。组织学观察创面再上皮化及巨噬细胞分布情况。采用qRT-PCR、western blotting、流式细胞术、免疫荧光和双荧光素酶报告基因检测等方法研究了Se@SiO2nanospheres调控巨噬细胞极化的机制。我们的研究结果表明，多孔Se@SiO2nanosphere-coated导管促进前列腺尿道的再上皮化，加速beagle犬TURP后伤口愈合，提高抗氧化能力，抑制氧化应激，诱导伤口巨噬细胞M2表型转变。多孔Se@SiO2nanospheres通过抑制活性氧（ROS）的功能，下调Ikk、i -κB和p65的磷酸化，阻断巨噬蛋白体外下游NF-κB通路。由于NF-κB信号级联的激活驱动巨噬细胞极化，多孔Se@SiO2nanospheres促进巨噬细胞表型从M1向M2转化。我们的研究结果表明，多孔Se@SiO2nanosphere-coated导管通过抑制ROS-NF-κB通路，促进巨噬细胞向M2表型极化，减轻炎症反应，从而促进前列腺尿道术后伤口恢复。良性前列腺增生（BPH）手术治疗后无法有效控制术后炎症反应仍然是研究人员和外科医生面临的一个挑战，因为它可能导致间接细胞死亡并最终延迟伤口愈合。伤口部位的巨噬细胞是局部炎症反应的关键调节因子。本研究设计并制作了一种新型多孔Se@SiO2nanosphere涂层导管，通过抑制ROS-NF-κB通路，将巨噬细胞极化向抗炎M2表型转移，从而促进前列腺尿道创面修复。这些结果表明，使用多孔Se@SiO2nanosphere-coated导管可以为前列腺尿道伤口愈合术后并发症提供一种治疗策略，以提高患者的生活质量。
Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophagesin vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response.Statement of SignificanceThe inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.