Effects of dutasteride in a rat model of chemically induced prostatic inflammation-Potential role of estrogen receptor β.
Effects of dutasteride in a rat model of chemically induced prostatic inflammation-Potential role of estrogen receptor β.
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DOI：
10.1002/pros.24071
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发表时间：
2020-12
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;Shin T;Wang Z;DeFranco DB;Yoshimura N;Mimata H
据报道，杜他雄胺可改善慢性组织学确定的前列腺炎症患者的下尿路症状，可能是通过激活雌激素受体β (ERβ)，其在前列腺组织中具有抗炎作用。因此，我们利用化学诱导的前列腺炎大鼠模型研究了度他雄胺对前列腺内炎症反应和膀胱活动的影响。选用10周龄雄性SD大鼠。在前列腺前叶注射5%福尔马林诱导前列腺炎症，对照组注射生理盐水（对照，n=5）。将前列腺炎症大鼠分为dutasteride治疗组（dutasteride, n=5）和安慰剂组（placebo, n=5）。从诱导前列腺炎症前2天开始，以每天0.5mg/kg的剂量给药杜他雄胺，而安慰剂大鼠只给药。28天后，在清醒状态下进行膀胱术，测量非排尿收缩（NVCs）、收缩间期（ICI）和排尿后残余容积（RV）。膀胱造瘘后，切除前列腺，qPCR检测ERα、ERβ、IL-1β、IL-18 mRNA表达水平。安慰剂组NVCs平均数目显著高于无前列腺炎的对照组（P<0.05）， ICI显著低于无前列腺炎的对照组（P<0.05）。相反，对照组和杜他雄胺组之间NVCs或ICI没有显著变化。三组间RV差异无统计学意义。安慰剂组大鼠ERα、IL-1β和IL-18基因表达水平显著高于对照组（P<0.05），而对照组与杜他雄胺组大鼠差异无统计学意义。另一方面，与对照组相比，安慰剂组大鼠ERβ mRNA表达水平显著降低（P<0.05），而杜他雄胺组大鼠ERβ mRNA表达水平无显著差异。杜他雄胺治疗不仅能改善前列腺炎症（IL-1β和IL-18基因表达水平增加），还能改善膀胱过度活动（膀胱充盈时NVCs增加）。这些治疗效果与抗炎ERβ的表达恢复有关。因此，杜他雄胺除了其先前已知的对良性前列腺增生的抗雄激素作用外，还可能通过调节ERβ来有效治疗前列腺炎症。
Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor β (ERβ), activation of which has anti-inflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation. Male SD rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (Control, n=5). Rats with prostatic inflammation were divided into dutasteride therapy (Dutasteride, n=5) and placebo groups (Placebo, n=5). Dutasteride was administrated at a dose of 0.5mg/kg daily from 2 days before induction of prostatic inflammation whereas Placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of mRNA expression levels of ERα, ERβ, IL-1β and IL-18 by qPCR. The mean number of NVCs was significantly greater in Placebo group than that of Control group without prostatic inflammation (P<0.05), and ICI were significantly decreased in Placebo group compared to Control group (P<0.05). On the contrary, there was no significant change in NVCs or ICI between Control and Dutasteride groups. RV was not significantly different among three groups. Gene expression levels of ERα, IL-1β and IL-18 was significantly increased in Placebo rats compared to Control rats (P<0.05), but not significantly different between Control and Dutasteride rats. On the other hand, the mRNA expression level of ERβ was significantly decreased in Placebo rats (P<0.05), but not in Dutasteride rats, compared to Control rats. Dutasteride treatment improved not only prostatic inflammation evident as increased gene expression levels in IL-1β and IL-18, but also bladder overactivity shown by increased NVCs during bladder filling. These therapeutic effects were associated with the restored expression of anti-inflammatory ERβ. Therefore, dutasteride might be effective via ERβ modulation for the treatment of prostatic inflammation in addition to its previously known, anti-androgenic effects on benign prostatic hyperplasia.
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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：
6.6
作者：
Dupont, MC;Spitsbergen, JM;Steers, WD
通讯作者：
Steers, WD
影响因子：
6.6
作者：
Vera, PL;Meyer-Siegler, KL
通讯作者：
Meyer-Siegler, KL
影响因子：
3.7
作者：
Cook LC;Hillhouse AE;Myles MH;Lubahn DB;Bryda EC;Davis JW;Franklin CL
通讯作者：
Franklin CL
影响因子：
23.4
作者：
Nickel, J. Curtis;Roehrborn, Claus G.;Rittmaster, Roger S.
通讯作者：
Rittmaster, Roger S.