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多孔 Se@SiO 纳米球涂层导管通过抑制活性氧-NF-κB 通路来调节巨噬细胞极化,从而加速前列腺尿道伤口愈合。

Porous Se@SiO nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

机构信息

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 650 Xin Songjiang Road, Shanghai 201620, China.

出版信息

Acta Biomater. 2019 Apr 1;88:392-405. doi: 10.1016/j.actbio.2019.02.006. Epub 2019 Feb 10.

DOI:10.1016/j.actbio.2019.02.006
PMID:30753941
Abstract

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO nanospheres 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@SiO nanospheres 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@SiO nanosphere-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@SiO nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO nanosphere-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 SIGNIFICANCE: The 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@SiO nanosphere 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@SiO nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.

摘要

良性前列腺增生 (BPH) 患者在手术后会出现并发症。我们研究了经尿道前列腺电切术 (TURP) 后前列腺尿道伤口愈合过程中多孔硒@二氧化硅纳米球对氧化应激的清除作用。建立 TURP 模型后,将比格犬随机分为两组。评估伤口恢复情况和氧化应激水平。通过组织学评估伤口部位的再上皮化和巨噬细胞分布。通过 qRT-PCR、western blot、流式细胞术、免疫荧光和双荧光素酶报告基因检测研究了多孔硒@二氧化硅纳米球调节巨噬细胞极化的机制。我们的结果表明,多孔硒@二氧化硅纳米球涂层导管可促进前列腺尿道的再上皮化,加速 TURP 后比格犬的伤口愈合,并提高抗氧化能力以抑制氧化应激,诱导伤口处巨噬细胞的 M2 表型转变。通过抑制活性氧 (ROS) 的功能,多孔硒@二氧化硅纳米球下调 Ikk、IκB 和 p65 磷酸化,从而阻断体外巨噬细胞中 NF-κB 通路的下游。由于 NF-κB 信号级联的激活驱动巨噬细胞极化,多孔硒@二氧化硅纳米球促进了巨噬细胞从 M1 向 M2 的表型转换。我们的研究结果表明,多孔硒@二氧化硅纳米球涂层导管通过抑制 ROS-NF-κB 通路促进巨噬细胞向 M2 表型转化,从而促进术后前列腺尿道伤口恢复,减轻炎症反应。

意义声明

良性前列腺增生 (BPH) 手术后,无法有效控制炎症反应仍然是研究人员和外科医生面临的挑战,因为这会导致间接细胞死亡,并最终延迟伤口愈合。伤口部位的巨噬细胞作为局部炎症反应的关键调节剂。在这里,我们设计并生产了一种新型多孔硒@二氧化硅纳米球涂层导管,并通过抑制 ROS-NF-κB 通路,将巨噬细胞向抗炎 M2 表型转化,从而证明了其在促进前列腺尿道伤口修复中的作用。这些结果表明,使用多孔硒@二氧化硅纳米球涂层导管可能为前列腺尿道伤口愈合过程中的术后并发症提供一种治疗策略,以提高患者的生活质量。

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