Department of Surgery, Taichung Armed Forces General Hospital, Taiwan.
Urology. 2011 Oct;78(4):971.e11-5. doi: 10.1016/j.urology.2011.05.050. Epub 2011 Aug 2.
To examine whether hypoxia occurs in the bladders of patients with interstitial cystitis (IC) by monitoring the expression of hypoxia-inducible factor-1 (HIF-1) and VEGF. Previous studies have reported that bladder perfusion is decreased in patients with IC. Hypoxia induces overexpression of vascular endothelial growth factor (VEGF), which has been reported to be associated with the formation of glomerulations in patients with IC.
The study group consisted of 32 patients with IC, and the control group consisted of 8 volunteers. We obtained bladder biopsies from both groups and studied the expression of HIF-1α and VEGF proteins by immunoblotting and immunohistochemical and double immunofluorescent staining. Data were analyzed using the Mann-Whitney U test.
Immunoblotting and immunostaining revealed that the expression of HIF-1α and VEGF proteins was increased in the study group compared with the control group. The relative intensities of HIF-1α and VEGF proteins were 60.60 ± 7.81 and 43.60 ± 5.37 in the study group and 26.20 ± 4.72 and 20.25 ± 1.45 in the control group, respectively. The overexpression of VEGF in study group biopsies was particularly evident in umbrella cells examined by confocal microscopy.
Our findings identified increased expression of HIF-1α in bladder tissue and overexpression of VEGF in umbrella cells from patients with IC. These events may be associated with glomerulation formation during hydrodistention in IC bladders. Thus, these molecular findings could offer the therapeutic mechanism for hyperbaric oxygenation application to patients with IC.
通过监测缺氧诱导因子-1(HIF-1)和血管内皮生长因子(VEGF)的表达,来研究间质性膀胱炎(IC)患者的膀胱是否存在缺氧。先前的研究报告称,IC 患者的膀胱灌注减少。缺氧会诱导血管内皮生长因子(VEGF)的过度表达,据报道,VEGF 与 IC 患者的肾小球形成有关。
研究组包括 32 名 IC 患者,对照组包括 8 名志愿者。我们从两组患者中获取膀胱活检组织,并通过免疫印迹、免疫组化和双重免疫荧光染色研究 HIF-1α 和 VEGF 蛋白的表达。采用 Mann-Whitney U 检验进行数据分析。
免疫印迹和免疫染色显示,与对照组相比,研究组 HIF-1α 和 VEGF 蛋白的表达增加。研究组 HIF-1α 和 VEGF 蛋白的相对强度分别为 60.60±7.81 和 43.60±5.37,对照组分别为 26.20±4.72 和 20.25±1.45。共聚焦显微镜检查发现,研究组活检标本中 VEGF 的过度表达尤其明显,伞细胞中表达增强。
本研究发现,IC 患者膀胱组织中 HIF-1α 的表达增加,伞细胞中 VEGF 的表达过度。这些事件可能与 IC 膀胱水扩张过程中的肾小球形成有关。因此,这些分子发现为高压氧治疗 IC 患者提供了治疗机制。