Lujan M, Ferruelo A, Paez A, Moreno A, Berenguer A
Department of Urology, Hospital de Getafe, Madrid, Spain.
BJU Int. 2004 Feb;93(3):410-4. doi: 10.1111/j.1464-410x.2003.04627.x.
To validate the spontaneous hypertensive rat (SHR) model for basic research into benign prostate hyperplasia (BPH), and to assess doxazosin-induced changes in prostatic structure and apoptotic status.
Four groups of rats were assessed: group 1, 15 SHRs treated with doxazosin; group 2, 14 SHRs with unilateral excision of the major pelvic ganglion; group 3, 14 untreated SHRs; and group 4, 16 intact Wistar-Kyoto (WKY) rats. The doxazosin mesylate (0.03 mg daily) was given compacted in rat food for 3 months. The prostatic ventral lobe (VL) was excised and weighed. Stereological light microscopy, multiplex reverse transcription-polymerase chain reaction of prostate caspases, and caspase-3 activity (cellular enzymatic assay) were assessed.
There was more development of the glandular epithelium (P < 0.001) in SHR rats than in controls, which was even greater after doxazosin exposure (P = 0.027). SHR animals had higher caspase expression (P < 0.05) and activity (P = 0.008) than WKY rats, but both were reduced after doxazosin therapy (P < 0.01 and 0.028, respectively).
This study confirmed prostate hyperplasia in the SHR model. Doxazosin exposure did not reduce the volume of glandular epithelium and contributed to protecting against caspase-induced apoptosis. The SHR model may be not a valid option to study doxazosin-induced apoptosis in BPH.
验证自发性高血压大鼠（SHR）模型用于良性前列腺增生（BPH）基础研究的可行性，并评估多沙唑嗪诱导的前列腺结构变化和凋亡状态。
评估四组大鼠：第1组，15只接受多沙唑嗪治疗的SHR；第2组，14只单侧切除主要盆腔神经节的SHR；第3组，14只未治疗的SHR；第4组，16只完整的Wistar-Kyoto（WKY）大鼠。将甲磺酸多沙唑嗪（每日0.03 mg）混入大鼠食物中给药3个月。切除前列腺腹叶（VL）并称重。进行体视学光学显微镜检查、前列腺半胱天冬酶的多重逆转录-聚合酶链反应以及半胱天冬酶-3活性（细胞酶学测定）评估。
与对照组相比，SHR大鼠的腺上皮发育更明显（P < 0.001），多沙唑嗪处理后更显著（P = 0.027）。SHR动物的半胱天冬酶表达（P < 0.05）和活性（P = 0.008）高于WKY大鼠，但多沙唑嗪治疗后均降低（分别为P < 0.01和0.028）。
本研究证实了SHR模型中存在前列腺增生。多沙唑嗪处理并未减少腺上皮体积，且有助于防止半胱天冬酶诱导的凋亡。SHR模型可能不是研究多沙唑嗪诱导的BPH凋亡的有效选择。
