Shabisgh A, Tanji N, D'Agati V, Burchardt M, Rubin M, Goluboff E T, Heitjan D, Kiss A, Buttyan R
Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Endocrinology. 1999 Apr;140(4):1920-6. doi: 10.1210/endo.140.4.6644.
Recent studies have found that blood flow to the rat ventral prostate gland is drastically reduced at an early time after castration. These observations caused us to reevaluate the effects of castration on the various cell populations of the ventral prostate, especially those in the prostatic vascular system. Sections of ventral prostate glands obtained at different times after castration were analyzed using the TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick END labeling) staining method to quantify apoptosis in different cell types. The results of this analysis showed a significant increase in TUNEL staining of prostate endothelial and (nonendothelial) stromal cells as early as 12 h postcastration that continued to 24 h after castration. In contrast, TUNEL labeling of prostate epithelial cells was not significantly increased compared with control values until 72 h after castration. The use of dual immunohistochemical staining procedures (anti-CD31 for endothelial cells or antismooth muscle actin for smooth muscle cells combined with TUNEL labeling) allowed us to confirm that the TUNEL-positive vascular cells at these early times after castration were endothelial in nature, whereas smooth muscle cells surrounding the prostate glands or portions of the afferent vascular endothelium were rarely TUNEL labeled. Electron microscopic evaluation of ventral prostate tissues at 48 h after castration provided further morphological evidence for the occurrence of apoptosis in prostate endothelial cells. Finally, the Lendrum-Fraser histochemical procedure used to identify fibrin leakage in tissues with vascular damage was applied to sections of the ventral prostate gland. This stain revealed diffuse fibrin accumulation in periglandular areas outside the capillaries and blood vessels in prostates from 24-h castrated rats, but not in prostates of sham-operated rats. Our results confirm an early effect of castration on the vascular system of the rat ventral prostate identified by increased apoptosis of endothelial cells and vascular leakiness. As these changes temporally precede the loss of epithelial cells, we propose that they may be causal rather than incidental to regression of the rat ventral prostate after castration.
近期研究发现,去势后早期大鼠腹侧前列腺的血流量急剧减少。这些观察结果促使我们重新评估去势对腹侧前列腺各种细胞群的影响,尤其是前列腺血管系统中的细胞群。采用TUNEL(末端脱氧核苷酸转移酶介导的dUTP缺口末端标记)染色法对去势后不同时间获取的腹侧前列腺切片进行分析,以量化不同细胞类型中的细胞凋亡情况。分析结果显示,早在去势后12小时,前列腺内皮细胞和(非内皮)基质细胞的TUNEL染色就显著增加,并持续至去势后24小时。相比之下,前列腺上皮细胞的TUNEL标记直到去势后72小时才与对照值相比显著增加。使用双重免疫组织化学染色程序(针对内皮细胞的抗CD31或针对平滑肌细胞的抗平滑肌肌动蛋白与TUNEL标记相结合)使我们能够确认,去势后这些早期时间点的TUNEL阳性血管细胞本质上是内皮细胞,而前列腺周围的平滑肌细胞或传入血管内皮的部分很少被TUNEL标记。对去势后48小时的腹侧前列腺组织进行电子显微镜评估,为前列腺内皮细胞凋亡的发生提供了进一步的形态学证据。最后,将用于识别血管损伤组织中纤维蛋白渗漏的Lendrum-Fraser组织化学程序应用于腹侧前列腺切片。该染色显示,在去势24小时的大鼠前列腺中,毛细血管和血管外的腺周区域有弥漫性纤维蛋白积聚,而假手术大鼠的前列腺中则没有。我们的结果证实了去势对大鼠腹侧前列腺血管系统的早期影响,其表现为内皮细胞凋亡增加和血管渗漏。由于这些变化在时间上先于上皮细胞的丢失,我们认为它们可能是大鼠去势后腹侧前列腺退化的原因而非偶然现象。