Gao Ye, Liu Peilin, He Fan, Yang Xingliang, Wu Ronghua, Chen Wei, Li Longkun, Yang Zhenxing
Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China.
Front Cell Dev Biol. 2021 Mar 30;9:630228. doi: 10.3389/fcell.2021.630228. eCollection 2021.
Non-invasive biomarkers to identify patients with bladder outlet obstruction (BOO)-related dysfunction are still needed to guide clinical practice. The current study aims to investigate molecular alterations and biomarkers associated with partial BOO (PBOO) in rats. Sprague-Dawley rats were used to establish the BOO model. Serum samples from 60 patients with benign prostatic hyperplasia (BPH) were used for enzyme-linked immunosorbent assay analysis. RNA sequencing and TMT-labeling proteomic analyses were conducted to identify molecular alterations. Masson's trichrome, H&E, and immunohistochemical staining and western blotting were conducted by using conventional methods following the manufacturer's instructions. Rats with PBOO experienced hypertrophy of smooth muscle cells and hyperplasia of interstitial cells during the first 4 weeks after the initiation of obstruction. Four weeks later, rats with PBOO showed activation of the adaptive immune response, cell death and apoptosis. The levels of brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) in the serum gradually increased in the first 4 weeks and gradually decreased after week 4. FGF2 levels slightly correlated with prostate volume ( = 0.156, = 0.0028) but not with age or BMI in BPH patients. No correlations were found between BDNF levels and prostate volume, age or BMI. BOO induces a change from bladder compensation to decompensation at week 4. FGF2 is involved in the development of hypertrophy in the PBOO bladder and shows a positive correlation with prostate volume in BPH patients.
仍需要非侵入性生物标志物来识别患有膀胱出口梗阻（BOO）相关功能障碍的患者，以指导临床实践。当前研究旨在调查与大鼠部分性BOO（PBOO）相关的分子改变和生物标志物。使用Sprague-Dawley大鼠建立BOO模型。采集60例良性前列腺增生（BPH）患者的血清样本进行酶联免疫吸附测定分析。进行RNA测序和TMT标记蛋白质组分析以识别分子改变。按照制造商的说明，采用常规方法进行Masson三色染色、苏木精-伊红染色、免疫组织化学染色和蛋白质免疫印迹。梗阻开始后的前4周，PBOO大鼠出现平滑肌细胞肥大和间质细胞增生。4周后，PBOO大鼠表现出适应性免疫反应激活、细胞死亡和凋亡。血清中脑源性神经营养因子（BDNF）和成纤维细胞生长因子2（FGF2）水平在最初4周逐渐升高，4周后逐渐下降。在BPH患者中，FGF2水平与前列腺体积轻度相关（r = 0.156，P = 0.0028），但与年龄或体重指数无关。未发现BDNF水平与前列腺体积、年龄或体重指数之间存在相关性。在第4周时，BOO会导致膀胱从代偿转变为失代偿。FGF2参与PBOO膀胱肥大的发展，并且在BPH患者中与前列腺体积呈正相关。
