Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Int Urogynecol J. 2021 Oct;32(10):2747-2755. doi: 10.1007/s00192-020-04472-5. Epub 2020 Aug 6.
Storage-phase bladder dysfunction can develop after pelvic radiotherapy. As the alpha-1d adrenoreceptor (a1d-AR) is dominant in the human detrusor, we aimed to investigate the effect of an a1d-AR antagonist on bladder dysfunction after pelvic radiotherapy in a rat model.
Twenty-four female Wistar rats were used. Eight rats (14-15 weeks, 250-300 g) were randomized to three groups (normal reference group, radiation alone group and radiation plus naftopidil group). An 18-Gy dose of radiotherapy was applied to the radiation alone and radiation plus naftopidil groups. Naftopidil (20 mg/kg) was administered daily to the radiation plus naftopidil group. Four weeks after radiation, all rats underwent cystometry and were killed for reverse transcription polymerase chain reaction to detect mRNAs [a1d-AR, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF)], Western blot to detect proteins (a1d-AR, extracellular-signal-regulated kinase, BDNF and VEGF) and immunohistochemistry.
Compared to the radiation alone group, (1) the decrease in the mRNA and protein expression of a1d-AR and VEGF was ameliorated, (2) the increase in the expression of BDNF mRNA and proteins such as extracellular-signal-regulated kinase and BDNF was suppressed, (3) submucosal thickness and vascularity on immunohistochemistry were improved, and (4) the baseline intravesical pressure and intercontraction interval in cystometry were ameliorated in the radiation plus naftopidil group.
Administration of an a1d-AR antagonist could improve storage-phase bladder dysfunction after radiotherapy not only by upregulating a1d-AR, which might decrease bladder compliance, but also by enhancing vascularity, which might protect the urinary bladder from chronic ischemic inflammation.
盆腔放疗后可出现贮尿期膀胱功能障碍。由于α1d-肾上腺素能受体（a1d-AR）在人类逼尿肌中占主导地位，我们旨在研究 a1d-AR 拮抗剂对大鼠模型盆腔放疗后膀胱功能障碍的影响。
使用 24 只雌性 Wistar 大鼠。8 只大鼠（14-15 周龄，250-300g）随机分为三组（正常参考组、单纯放疗组和放疗加萘哌地尔组）。单纯放疗组和放疗加萘哌地尔组给予 18Gy 剂量放疗。放疗加萘哌地尔组每日给予萘哌地尔（20mg/kg）。放疗后 4 周，所有大鼠行膀胱测压并处死，行逆转录聚合酶链反应检测 mRNAs[a1d-AR、脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）]、Western blot 检测蛋白（a1d-AR、细胞外信号调节激酶、BDNF 和 VEGF）和免疫组织化学。
与单纯放疗组相比，（1）a1d-AR 和 VEGF 的 mRNA 和蛋白表达下降得到改善，（2）BDNF mRNA 表达及细胞外信号调节激酶和 BDNF 等蛋白表达受到抑制，（3）免疫组织化学中黏膜下厚度和血管生成得到改善，（4）膀胱测压中基础膀胱内压和收缩间期得到改善。
a1d-AR 拮抗剂的给药不仅通过下调逼尿肌中可能降低膀胱顺应性的 a1d-AR，而且通过增强血管生成来改善放疗后贮尿期膀胱功能障碍，后者可能保护膀胱免受慢性缺血性炎症的影响。
