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非那雄胺通过 DHT 和 AR 信号通路加速铥激光切除术后前列腺伤口愈合。

Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

机构信息

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

Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China.

出版信息

Cell Prolif. 2018 Jun;51(3):e12415. doi: 10.1111/cpr.12415. Epub 2017 Nov 30.

DOI:10.1111/cpr.12415
PMID:29194865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6528864/
Abstract

OBJECTIVES

Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling.

MATERIALS AND METHODS

TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated.

RESULTS

Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction.

CONCLUSION

Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization.

摘要

目的

尿路上皮感染、尿频、尿急、尿道痛和出血是经钬激光前列腺切除术(TmLRP)后的常见术后并发症。我们的研究主要集中在通过 AR 信号转导研究非那雄胺在前列腺伤口愈合中的作用。

材料与方法

将 TmLRP 比格犬随机分为不同的治疗组。测定血清和前列腺内睾酮和 DHT 水平。进行组织学分析以研究各组前列腺尿道的再上皮化和炎症反应。我们研究了雄激素在前列腺增殖和炎症反应中的作用。此外,还研究了 TNF-α 对前列腺上皮细胞和基质细胞的作用。

结果

睾酮组的睾酮和 DHT 水平升高,非那雄胺组的 DHT 降低。非那雄胺组前列腺尿道愈合加快。DHT 抑制前列腺上皮细胞的增殖并增强前列腺中的炎症反应。我们证实 DHT 通过 AR 信号转导增强巨噬细胞 TNF-α 的分泌。TNF-α 抑制前列腺上皮细胞的增殖并延迟细胞迁移。TNF-α在抑制成纤维细胞激活和收缩方面也起着关键作用。

结论

睾酮治疗抑制了前列腺尿道的再上皮化和愈合。非那雄胺治疗可能是促进前列腺再上皮化的有效方法。

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本文引用的文献

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Prostate. 2017 May;77(7):708-717. doi: 10.1002/pros.23301. Epub 2017 Feb 7.
2
Suppression of NRF2-ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells.抑制NRF2-ARE活性可增强化疗药物对人急性单核细胞白血病细胞的细胞毒性作用。
Toxicol Appl Pharmacol. 2016 Feb 1;292:1-7. doi: 10.1016/j.taap.2015.12.008. Epub 2015 Dec 18.
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Tumor necrosis factor receptor 1 functions as a tumor suppressor.肿瘤坏死因子受体 1 作为肿瘤抑制因子发挥作用。
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