前列腺术后创面修复过程中雄激素受体信号通路调控前列腺上皮基底细胞及其微环境的作用及机制研究

The poor wound healing is the key factor resulting several complications after mini-invasive operation for benign prostatic hyperplasia (BPH), but the mechanisms underlying and the regulating factors are largely unknown. Our previous results showed that the re-epithelialization of the prostate wound results from prostate basal cells, but not from the urothelium of the resection margin of the bladder neck. Furthermore, we found that castration could promote the operating wound healing of the prostate. It has been reported that androgen receptor (AR) inhibits the proliferation of the prostate basal cells, and we and other researchers found there is a complex cross-talk between AR signaling and macrophage, the key component of the traumatic microenvironment. Based on these results, we hypothesize that AR signaling inhibits the process of prostate wound repair through regulating the proliferation of the basal cell and the microenvironment. In this study, we will establish the canine model of Thulium laser resection of the prostate (TmLRP), and then observe the influence of the androgen on re-epithelialization and the microenvironment. What’s more, we will study the regulation and the mechanisms of AR signaling on prostate basal cell and the components of microenvironment using co-culture and gene chip and protein chip. The ultimate objective of this study is to demonstrate the role of androgen and AR in the process of prostate wound repair, and to provide a new insight for the treatment of the complications of prostate operation.

良性前列腺增生症微创手术后创面愈合不良是导致一系列术后并发症的关键因素，但前列腺创面修复的分子机制及其调控因素仍不清楚。课题组前期研究发现前列腺创面再生上皮来源于残存前列腺组织中基底细胞的增殖、分化，而非传统认为的膀胱颈部切缘尿路上皮的爬行覆盖，并进一步发现去势可促进创面恢复。雄激素受体（AR）信号通路能抑制前列腺基底细胞增殖，且与创面微环境的核心组分巨噬细胞之间存在cross-talk。据此我们提出假设：AR信号通路可能通过调控前列腺基底细胞及其微环境对前列腺术后创面修复发挥抑制作用。本课题拟在建立犬铥激光前列腺切除模型的基础上，观察雄激素对创面再上皮化及其微环境的影响；利用细胞共培养结合基因芯片和蛋白芯片技术，研究AR信号通路对前列腺基底细胞及创面微环境各组分的调控作用及机制。最终阐明雄激素及其受体在前列腺创面修复中的作用及分子机制，为前列腺术后并发症的防治提供新的思路。

良性前列腺增生症微创手术后创面愈合不良是导致一系列术后并发症的关键因素，但前列腺创面修复的分子机制及其调控因素仍不清楚。课题组前期研究发现前列腺创面再生上皮来源于残存前列腺组织中基底细胞的增殖、分化，而非传统认为的膀胱颈部切缘尿路上皮的爬行覆盖，并进一步发现去势可促进创面恢复。雄激素受体（AR）信号通路能抑制前列腺基底细胞增殖，且与创面微环境的核心组分巨噬细胞之间存在cross-talk。本课题组研究发现：AR信号通路可通过调控前列腺基底细胞及其微环境对前列腺术后创面修复发挥抑制作用。本课题在建立犬铥激光前列腺切除模型的基础上，观察雄激素对创面再上皮化及其微环境的影响；进一步研究了AR信号通路对前列腺基底细胞及创面微环境各组分的调控作用及机制。最终阐明了雄激素及其受体在前列腺创面修复中的作用及分子机制，为前列腺术后并发症的防治提供新的思路。

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