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| 發表人 | 討論主題 | 發表時間 | 討論數 |
| 林登龍 | Sasatomi, K., Hiragata, S., Miyazato, M. et al.: Nitric oxide-mediated suppression of detrusor overactivity by arginase inhibitor in rats with chronic spinal cord injury. | 2008/9/30 下午 07:18:27 | 0 |
| 原 文 | 題 目 | Sasatomi, K., Hiragata, S., Miyazato, M. et al.: Nitric oxide-mediated suppression of detrusor overactivity by arginase inhibitor in rats with chronic spinal cord injury. |
| 作 者 | 林登龍 | |
| 出 處 | Urology, 72: 696, 2008. | |
| 出版日期 | Urology, 72: 696, 2008. | |
| 評 論 | 脊髓損傷導致膀胱逼尿肌過度活動的產生至目前為止，仍然不是完全了解，因此治療效果一直不理想。過去治療重點放在膀胱 muscarinic receptor， 藥物使用 anti-muscarinics，但是仍只能部分改善。 本文則探討一氧化氮(nitric oxide; NO)於脊髓損傷導致膀胱逼尿肌過度活動所扮演的角色。NO 於膀胱可鈍化膀胱感覺，改善膀胱過動。製造NO 的材料為 arginine，使用arginase inhibitor 可增加arginine 含量，進而提升NO的產生。本文研究發現大白鼠脊髓損傷後，膀胱逼尿肌過度活動，而且膀胱組織中 arginase 表現增加，可能因此造成 NO產量減少。使用arginase inhibitor 後增加arginine 含量，進而提升NO的產生，而使膀胱逼尿肌過度活動得到改善。此研究結果如能於臨床得到證實，則是脊髓損傷病人的重大福音。 | |
| abstract |
We investigated the effects of an arginase inhibitor on bladder overactivity and measured bladder arginase I and II mRNA levels in rats with chronic spinal cord injury (SCI). METHODS We performed awake cystometrograms 3 to 4 weeks after spinal cord transection in female rats. Cystometric parameters such as mean amplitudes and number of non-voiding contractions (NVCs), voided volume, voiding efficiency, and micturition pressure were evaluated before and after intravenous (IV) injection of an arginase inhibitor (nor-NOHA: N_-hydroxy-nor-Larginine) in SCI rats. We also examined the effects of an NOS inhibitor (L-NAME: N_-nitro- L-arginine methyl ester hydrochloride) to determine whether suppression of bladder overactivity by arginase inhibition is mediated by increased production of NO. In addition, we measured mRNA levels of arginase I and II in SCI bladders using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS We found that nor-NOHA (10 mg/kg, IV) significantly decreased the amplitude and number of NVCs. There were no significant changes in other parameters before and after administration of vehicle or nor-NOHA at any dose. When we administered L-NAME (20 mg/kg, IV) before nor-NOHA injection (10 mg/kg, IV), nor-NOHA–induced inhibition of NVCs was prevented. The relative levels of both arginase I and II mRNA in the bladder were significantly higher in SCI rats compared with spinal cord–intact rats. CONCLUSIONS These results suggest that arginase inhibition can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, arginase inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI. |
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