Study in the role of nitric oxide (NO) and advanced glycation end products (AGE) on bladder function

一氧化氮（NO）和晚期糖基化终产物（AGE）对膀胱功能作用的研究

• 批准号: 11671563
• 负责人: YOSHIDA Masaki
• 金额: $ 1.98万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671563/
• 关键词: Nitric oxide (NO); AGE; NOS; Acetylcholine; Bladder smooth muscle; Nitrergic nerve; Aging; Spinal cord injury; Nitric oxide; NO消去剤; 膀胱平滑筋; 加齢; 尿失禁; 尿道平滑筋; 膀胱; 脊髄損傷; 腎機能

Nitric oxide (NO) is one of the most important molecules for regulation of lower urinary tract function in the physiological and pathophysiological conditions. Furthermore, it has been demonstrated that advanced glycation end products (AGE) contributes to damages of the cellular function through the AGE-receptors in various tissues. In this study, we have evaluated the role of NO and AGE on bladder function.In rat and human detrusor specimens, NADPH-diaphorase staining and nNOS immunohistochemical staining showed the NADPH-positive and nNOS-positive neurons, which are significantly less as compared to urethral and prostatic specimensIn the functional experiments, electrical field stimulation (EFS) did not cause significant relaxation responses in smooth muscle strips isolated from human and rabbit bladder precontracted with carbachol. However, L-NNA (a NOS inhibitor) caused a significant increase in EFS-induced acetylcholine (ACh) release from cholinergic nerve endings in the rabbit bl … More adder. The data suggest that NO has an inhibitory action on ACh release in bladder, which may cause increase in bladder capacity and decrease in detrusor instability in the filling phase of micturition cycle.There were AGE formations in human detrusor specimens. The formation was significantly higher in the aged patients, and there was significant positive correlation between age and AGE formation. In contrast, nNOS histochemical staining and NO release induced by EFS in human detrusor smooth muscles were significantly decreased with age. And, there was a negative correlation between AGE formation and NO release. In rats with spinal cord injury, NO release induced by EFS was significantly decreased, and AGE formation was significantly increased in the bladder, as compared to bladder of the control rat.The data may suggest that there was significant relationship between AGE formation and NO release/NOS activity in bladder function in physiological and pathophysiological conditions. However, further studies are needed to evaluate the mechanism of the relationship for bladder function. Less

在生理和病理生理条件下，一氧化氮(NO)是调节下尿路功能的重要分子之一。此外，已证实晚期糖基化终产物(AGE)通过多种组织中的AGE受体参与细胞功能的损害。本研究探讨了NO和AGE对膀胱功能的影响。在大鼠和人逼尿肌标本中，NADPH黄递酶和nNOS免疫组织化学染色显示NADPH阳性神经元和nNOS阳性神经元明显少于尿道和前列腺标本。在功能实验中，电场刺激(EFS)对卡巴胆碱预收缩的人和兔膀胱平滑肌条没有明显的松弛反应。然而，一氧化氮合酶抑制剂L可显著增加电针刺激引起的兔…胆碱能神经末梢的乙酰胆碱(ACh)释放更糟的是。提示NO对膀胱ACh释放有抑制作用，可能导致膀胱容量增加，排尿周期充盈期逼尿肌不稳定程度降低。老年患者的年龄与年龄呈显著正相关。而人逼尿肌nNOS组织化学染色和EFS诱导的NO释放则随增龄而明显减少。AGE的形成与NO的释放呈负相关。与对照组相比，脊髓损伤大鼠膀胱组织中EFS诱导的NO释放明显减少，AGE生成明显增加，提示AGE的形成与膀胱功能的NO释放/NOS活性在生理和病理生理条件下存在显著的相关性。然而，还需要进一步的研究来评估这种关系对膀胱功能的影响机制。较少

项目成果

Yoshida Masaki: "Effects of prstaglandin E_2 receptors antagonist in overacitive bladder in the chronic spinal rats"Neurourology and Urodynamics. 19(4). 407-408 (2000)

吉田正树：“前列腺素 E_2 受体拮抗剂对慢性脊髓大鼠膀胱过度活动症的影响”神经泌尿学和尿动力学。

Yoshida, M., Murakami, S., Yono, M., Seshita, H., Miyamoto, Y., Inadome, A., Miyamae, K., Iwashita, H., Ueda, S.: "Pharmacological effects of a new muscarinic receptors antagonist : KRP-197 on isolated human urinary bladder"Neurourology and Urodynamics. 1

Yoshida, M.、Murakami, S.、Yono, M.、Seshita, H.、Miyamoto, Y.、Inadome, A.、Miyamae, K.、Iwashita, H.、Ueda, S.：“

Seshita, H.. Yoshida, M., Takahashi, W., Inadome, A., Yono, M., Miyamoto, Y., Murakami, S., Ueda.S.: "Prejunctional α-adrenoceptors regulate nitrergic neurotransmission in the rabbit urethra."Eur.J.Pharmacol.. 400. 271-278 (2000)

Seshita, H.. Yoshida, M.、Takahashi, W.、Inadome, A.、Yono, M.、Miyamoto, Y.、Murakami, S.、Ueda.S.：“结前 α-肾上腺素能受体调节硝化神经传递兔尿道。”Eur.J.Pharmacol.. 400. 271-278 (2000)

Yono, M., Yoshida, M., Takahashi, W., Inadome, A., Ueda, S.: "Comprison of the effects of novel antimuscarinic drugs on human detrusor smooth muscle."Br.J.Urol.. 86(6). 719-725 (2000)

Yono，M.，Yoshida，M.，Takahashi，W.，Inadome，A.，Ueda，S.：“新型抗毒蕈碱药物对人类逼尿肌平滑肌的影响的比较。”Br.J.Urol.. 86（

Masaki Yoshida: "Age-related changes in acetylcholine and adenosine triphosphate releases from human bladder smooth muscles"Neurourology and Urodynamics. 18. 346-347 (1999)

Masaki Yoshida：“人类膀胱平滑肌释放的乙酰胆碱和三磷酸腺苷的年龄相关变化”神经泌尿学和尿动力学。