Inhibitory effect of α1D/1A antagonist 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide on estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo
Inhibitory effect of α1D/1A antagonist 2-(1H-indol-3-yl)-N-[3-(4-(2-methoxyphenyl) piperazinyl) propyl] acetamide on estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo
复制标题
α(1D/1A)拮抗剂2-(1H-吲哚-3-基)-N-[3-(4-(2-甲氧基苯基)哌嗪基)丙基]乙酰胺对雌/雄激素诱导的大鼠良性前列腺增生的抑制作用
DOI：
10.1016/j.ejphar.2019.172817
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发表时间：
2020-03-05
影响因子：
5
通讯作者：
Huang, Jun-jun
中科院分区：
文献类型：
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作者：
Liu, Qi-meng;Xiao, Qing;Huang, Jun-jun
良性前列腺增生（BPH）是老年男性泌尿系统的一种常见疾病。由萘托地尔衍生的2-（1h -吲哚-3-基）- n[3-（4-（2甲氧基苯基）哌嗪基）丙基]乙酰胺（HJZ-3）对am肾上腺素的体外抑制作用分别比α (1B)-和α (1A)-肾上腺素的体外抑制作用高97.7倍和64.6倍。为了探讨HJZ-3对BPH的治疗潜力，我们对其药理活性进行了评价。具体来说，我们通过雌激素/雄激素诱导的大鼠体内良性前列腺增生模型进行了评估。HJZ-3通过抑制前列腺指数的升高，降低相对腺泡体积、相对间质、上皮体积、上皮厚度的定量分析以及增殖细胞核抗原、a-平滑肌肌动蛋白的表达，有效阻止大鼠前列腺增生的进展。HJZ-3降低了前列腺组织中α (1A)-和α (1D)-肾上腺素受体蛋白的表达。HJZ-3是一个很好的替代α (1A)-和α (1D)-肾上腺素受体阻滞剂。它可以放松平滑肌张力，缓解前列腺增生的症状。
Benign prostatic hyperplasia (BPH) is a common disorder of the urinary system in aging men. 2-(1H-indol-3-yl)-N[3-(4-(2 methoxyphenyl) piperazinyl) propyl] acetamide (HJZ-3), which is derived from naftopidil, exhibited 97.7- and 64.6-fold greater inhibitory effects for a m adrenoceptor than for alpha(1B)- and alpha(1A)-adrenoceptors in vitro, respectively. To investigate the therapeutic potential for treating BPH, we evaluated the pharmacological activity of HJZ-3. Specifically, we evaluated through estrogen/androgen-induced rat benign prostatic hyperplasia model in vivo. HJZ-3 effectively prevented the progression of rat prostatic hyperplasia by suppressing the increase in prostate index and reducing the quantitative analysis of the relative acinus volume, relative stroma, epithelial volume and epithelial thickness and expression of proliferating cell nuclear antigen and a-smooth muscle actin. HJZ-3 decreased alpha(1A)- and alpha(1D)-adrenoceptor protein expressions in prostate tissue. HJZ-3 is a good alternative for alpha(1A)- and alpha(1D)-adrenoceptor blocker. It may relax smooth muscle tone and relieve symptoms of BPH.