Gray Katherine T, Ventura Sabatino
Department of Pharmaceutical Biology and Pharmacology, Faculty of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
J Pharmacol Toxicol Methods. 2005 Jan-Feb;51(1):41-50. doi: 10.1016/j.vascn.2004.07.001.
Research into prostate development and function is mainly carried out in rats and guinea pigs. While these animals have proven to be good models of human prostate function, their use is limited when compared with what could be achieved using the various currently available gene knockout mice. This study aimed to ascertain whether the mouse prostate was a viable model for studying human prostate function.
Sections from mouse prostate glands were histochemically processed to visualise the neurotransmitters and receptors present. Isolated organ bath studies were conducted in Krebs-Henseleit solution at 37 degrees C to delineate the physiological mechanisms involved in contractility.
Positive histochemical staining for noradrenaline and acetylcholinesterase (AChE) was observed in the fibromuscular stroma. AChE-positive staining was also observed in epithelial cells lining prostatic acini. Immunoreactivity to P2X(1) and P2X(7) purinoceptors was observed in the fibromuscular stroma and immunoreactivity to P2X(4) purinoceptors in the glandular epithelium. Positive immunostaining for neuropeptide Y, big endothelin, calcitonin gene-related peptide (CGRP), substance P, and neurokinin A was observed in the fibromuscular stroma. Frequency-response curves (1.0 ms pulse duration, 60 V, 0.1-20 Hz) to electrical field stimulation yielded frequency-dependent contractions that were attenuated by tetrodotoxin (P < .001), guanethidine (P < .001), and prazosin (P = .01). Suramin (P = .21), alpha,beta-methylene ATP (P = .84), and atropine (P = .76) caused no significant effects. Concentration-response curves to endogenously administered phenylephrine yielded concentration-dependent contractions (pEC(50) = 6.1 +/- 0.3, maximum response 0.20 +/- 0.03 g), which were attenuated by prazosin (P < .001).
Histochemistry suggests that mouse prostates have a similar innervation to that of humans and other laboratory animals. Furthermore, responses to nerve stimulation are noradrenergic and mediated by alpha(1)-adrenoceptors. Therefore, the mouse prostate is a suitable model for human prostate function and a viable isolated preparation for contractility studies.
前列腺发育与功能的研究主要在大鼠和豚鼠身上进行。虽然这些动物已被证明是人类前列腺功能的良好模型，但与使用目前各种可用的基因敲除小鼠所能达到的效果相比，它们的应用受到限制。本研究旨在确定小鼠前列腺是否是研究人类前列腺功能的可行模型。
对小鼠前列腺组织切片进行组织化学处理，以观察其中存在的神经递质和受体。在37℃的克氏-亨氏溶液中进行离体器官浴研究，以阐明参与收缩性的生理机制。
在纤维肌性基质中观察到去甲肾上腺素和乙酰胆碱酯酶（AChE）的阳性组织化学染色。在前列腺腺泡内衬的上皮细胞中也观察到AChE阳性染色。在纤维肌性基质中观察到对P2X(1)和P2X(7)嘌呤受体的免疫反应性，在腺上皮中观察到对P2X(4)嘌呤受体的免疫反应性。在纤维肌性基质中观察到神经肽Y、大内皮素、降钙素基因相关肽（CGRP）、P物质和神经激肽A的阳性免疫染色。电场刺激的频率-反应曲线（脉冲持续时间1.0毫秒，60伏，0.1 - 20赫兹）产生频率依赖性收缩，这些收缩被河豚毒素（P <.001）、胍乙啶（P <.001）和哌唑嗪（P =.01）减弱。苏拉明（P =.21）、α,β-亚甲基ATP（P =.84）和阿托品（P =.76）无显著影响。对内源性给予去氧肾上腺素的浓度-反应曲线产生浓度依赖性收缩（pEC(50) = 6.1 ± 0.3，最大反应0.20 ± 0.03克），该收缩被哌唑嗪减弱（P <.001）。
组织化学表明小鼠前列腺的神经支配与人类和其他实验动物相似。此外，对神经刺激的反应是去甲肾上腺素能的，并由α(1)-肾上腺素受体介导。因此，小鼠前列腺是研究人类前列腺功能的合适模型，也是用于收缩性研究的可行离体标本。
