Effects of Estrogen Receptor β Stimulation in a Rat Model of Non-Bacterial Prostatic Inflammation.
Effects of Estrogen Receptor β Stimulation in a Rat Model of Non-Bacterial Prostatic Inflammation.
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DOI：
10.1002/pros.23320
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Mimata H
中科院分区：
文献类型：
--
作者：
Mizoguchi S;Mori K;Wang Z;Liu T;Funahashi Y;Sato F;DeFranco DB;Yoshimura N;Mimata H
越来越多的证据表明，慢性非细菌性前列腺炎症参与了良性前列腺增生（BPH）和男性下尿路症状（LUTS）的发病机制。雌激素受体β（estrogen receptor β，ERβ）在前列腺组织中具有免疫保护作用。因此，我们在非细菌性前列腺炎症大鼠模型中研究了ERβ激活不仅对前列腺炎症，而且对膀胱过度活动状态的影响。雄性Sprague-Dawley大鼠（8周，n = 15）被分为三组：假盐水组（n = 5）、福尔马林载体组（n = 5）和福尔马林处理组（n = 5）。假生理盐水组行假手术，前列腺腹侧叶注射生理盐水50 μl。福尔马林-溶剂组在前列腺两侧腹叶注射50 μl 5%福尔马林。福尔马林处理组在诱导前列腺炎症前2天开始接受3α-Adiol（一种选择性ERβ激动剂前体）治疗，剂量为3 mg/kg/天，而福尔马林溶剂大鼠接受溶剂（橄榄油）。各组在前列腺内注射福尔马林或假手术后第28天进行清醒膀胱测压。膀胱测压后，收获膀胱和前列腺用于mRNA表达评估和组织学分析。膀胱测压结果显示，福尔马林组大鼠的平均非排尿性收缩次数显著多于假盐水组，排尿间隔显著缩短（P < 0.05）。RT-qPCR结果显示，与假盐水组相比，福尔马林组大鼠膀胱黏膜中NGF、P2 X2和TRPA 1受体mRNA表达显著增加，前列腺腹叶中TNF-α、iNOS和COX 2 mRNA表达显著增加（P <0. 05）。福尔马林组大鼠前列腺腹叶ERβ/ERα mRNA表达的相对比值（ERβ/ERα）较假盐水组显著降低（P < 0.05）。在福尔马林处理的大鼠中给予3α-Adiol可改善这些变化。这些结果表明，通过给予3α-Adiol激活ERβ，使前列腺中ERβ/ERα表达比例正常化，不仅可以改善前列腺炎症，而且可以改善膀胱过度活动。因此，ERβ激动剂可能有助于治疗伴有前列腺炎症的症状性BPH患者的膀胱刺激症状。
There is increasing evidence showing that chronic non-bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor β (ERβ) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ERβ-activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation. Male Sprague-Dawley rats (8 weeks, n = 15) were divided into three groups: sham-saline group (n = 5), formalin-vehicle group (n = 5), and formalin-treatment group (n = 5). The sham-saline group had sham operation and 50 μl normal saline injected into each ventral lobe of the prostate. The formalin-vehicle group had 50 μl 5% formalin injection into bilateral ventral lobes of the prostate. The formalin-treatment group was treated with 3α-Adiol (a selective ERβ agonist precursor) at a dose of 3 mg/kg daily from 2 days before induction of prostatic inflammation, whereas formalin-vehicle rats received vehicle (olive oil). In each group, conscious cystometry was performed on day 28 after intraprostatic formalin injection or sham treatment. After cystometry, the bladder and prostate were harvested for evaluation of mRNA expression and histological analysis. In cystometric investigation, the mean number of non-voiding contractions was significantly greater and voiding intervals were significantly shorter in formalin-vehicle rats than those in sham-saline rats (P < 0.05). In RT-qPCR analysis, mRNA expression of NGF, P2X2, and TRPA1 receptors was significantly increased in the bladder mucosa, and mRNA expression of TNF-α, iNOS and COX2 in the ventral lobes of prostate was significantly increased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). In addition, relative mRNA expression ratio of ERβ to ERα (ERβ/ERα) in the ventral lobes of prostate was significantly decreased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). These changes were ameliorated by 3α-Adiol administration in formalin-treatment rats. These results indicate that ERβ activation by 3α-Adiol administration, which normalized the ERβ/ERα expression ratio in the prostate, can improve not only prostatic inflammation, but also bladder overactivity. Therefore, ERβ agonists might be useful for treating irritative bladder symptoms in patients with symptomatic BPH associated with prostatic inflammation.
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影响因子：
7.4
作者：
DeBerry JJ;Schwartz ES;Davis BM
通讯作者：
Davis BM
DOI：
10.1158/1940-6207.capr-13-0276
发表时间：
2014-02
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Chaudhary SC;Singh T;Talwelkar SS;Srivastava RK;Arumugam A;Weng Z;Elmets CA;Afaq F;Kopelovich L;Athar M
通讯作者：
Athar M
影响因子：
2.8
作者：
Funahashi, Yasuhito;O'Malley, Katherine J.;Kawamorita, Naoki;Tyagi, Pradeep;DeFranco, Donald B.;Takahashi, Ryosuke;Gotoh, Momokazu;Wang, Zhou;Yoshimura, Naoki
通讯作者：
Yoshimura, Naoki
影响因子：
2.6
作者：
Meng, Mingsen;Zheng, Ji;Li, Weibing
通讯作者：
Li, Weibing
影响因子：
6.6
作者：
Dupont, MC;Spitsbergen, JM;Steers, WD
通讯作者：
Steers, WD