Konkol Yvonne, Vuorikoski Heikki, Streng Tomi, Tuomela Johanna, Bernoulli Jenni
Cancer Research Laboratory, FICAN West, Institute of Biomedicine, University of Turku, Turku, Finland.
Pharmatest Services Ltd., Turku, Finland.
Transl Androl Urol. 2019 Mar;8(Suppl 1):S45-S57. doi: 10.21037/tau.2019.02.03.
Chronic nonbacterial prostatitis associated with lower urinary tract symptoms (LUTS) is a prevalent condition in men. One potential pathophysiological factor is change in sex hormone, testosterone and estrogen, balance. Inflammation, cancer and obstructive voiding has been induced in the Noble rat strain by altering levels of sex hormones. We evaluated if imbalance of sex hormones could induce comparable diseases also in a less estrogen sensitive Wistar strain rats.
Subcutaneous testosterone (830 µg/day) and 17β-estradiol (83 µg/day) hormone pellets were used in male Wistar and Noble strain rats to induce prostatic diseases. The rats were followed for 13 and 18 weeks. Urodynamical measurements were performed at the end of the study under anesthesia. Prostates were collected for further histological analysis. A panel of cytokines were measured from collected serum samples.
Noble rats exhibited stromal and glandular inflammation after 13 weeks that progressed into more severe forms after 18 weeks of hormonal treatment. CD68-positive macrophages were observed in the stromal areas and inside the inflamed acini. CD163-positive macrophages were present in the stromal compartment but absent inside inflammatory foci or prostate acini. Thirteen-week hormonal treatment in Noble rats induced obstructive voiding, which progressed to urinary retention after 18-weeks treatment. In the Wistar rats 18-week treatment was comparable to the 13-week-treated Noble rats judged by progression of prostatic inflammation, being also evident for obstructive voiding. Incidence of PIN-like lesions and carcinomas in the periurethal area in Noble rats were high (100%) but lower (57%) and with smaller lesions in Wistar rats. Serum cytokines leptin, CCL5, and VEGF concentrations showed a decrease in the hormone-treated rats compared to placebo-treated rats.
Prostate inflammation and obstructive voiding developed also in the Wistar rats but more slowly than in Noble rats. Male non-castrated Wistar strain rats may thus be suitable to use in studies of pathophysiology and hormone-dependent prostate inflammation and obstructive voiding.
伴有下尿路症状（LUTS）的慢性非细菌性前列腺炎在男性中很常见。一个潜在的病理生理因素是性激素、睾酮和雌激素平衡的改变。通过改变性激素水平，已在诺布尔大鼠品系中诱发了炎症、癌症和排尿梗阻。我们评估了性激素失衡是否也能在对雌激素不太敏感的Wistar品系大鼠中诱发类似疾病。
在雄性Wistar和诺布尔品系大鼠中使用皮下注射睾酮（830μg/天）和17β-雌二醇（83μg/天）激素丸来诱发前列腺疾病。对大鼠进行了13周和18周的跟踪观察。在研究结束时，在麻醉下进行尿动力学测量。收集前列腺进行进一步的组织学分析。从收集的血清样本中测量一组细胞因子。
诺布尔大鼠在13周后出现基质和腺体炎症，在激素治疗18周后发展为更严重的形式。在基质区域和发炎的腺泡内观察到CD68阳性巨噬细胞。CD163阳性巨噬细胞存在于基质区，但在炎症灶或前列腺腺泡内不存在。对诺布尔大鼠进行13周的激素治疗会诱发排尿梗阻，在18周治疗后发展为尿潴留。在Wistar大鼠中，根据前列腺炎症的进展判断，18周的治疗与13周治疗的诺布尔大鼠相当，排尿梗阻也很明显。诺布尔大鼠尿道周围区域的PIN样病变和癌的发生率很高（100%），但Wistar大鼠较低（57%）且病变较小。与安慰剂治疗的大鼠相比，激素治疗的大鼠血清细胞因子瘦素、CCL5和VEGF浓度降低。
Wistar大鼠也出现了前列腺炎症和排尿梗阻，但比诺布尔大鼠发展得更慢。因此，雄性未阉割的Wistar品系大鼠可能适用于病理生理学以及激素依赖性前列腺炎症和排尿梗阻的研究。
