Shimizu Shogo, Saito Motoaki, Kinoshita Yukako, Kazuyama Emi, Tamamura Mayuko, Satoh Itaru, Satoh Keisuke
Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Yonago City, Tottori, Japan.
BJU Int. 2009 Sep;104(5):713-7. doi: 10.1111/j.1464-410X.2009.08471.x. Epub 2009 Mar 30.
To investigate the effect of a free-radical scavenger, edaravone, on the changes occurring with acute urinary retention (AUR) and subsequent catheterization in the rat bladder.
Eight-week-old male Sprague Dawley rats were allocated to one of four groups; an AUR group that had urinary retention induced, with subsequent catheterization; two edaravone groups, given edaravone at 1 or 10 mg/kg body weight for 60 min and then the same urinary retention and subsequent catheterization; and a sham-operated control group given edaravone 10 mg/kg. Urinary retention was induced by the clamping the rat penile urethra with a small clip, making a cystostomy, and then infusing 3 mL (0.6 mL/min) of saline with an infusion pump. The obstruction was sustained for 30 min and then the bladder was allowed to drain with a catheter in place for 60 min as the studies continued. After killing the rats the function of the bladder was assessed, with carbachol and 100 mM KCl, and the levels of malondialdehyde (MDA, a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative DNA damage), heat-shock protein 70 (HSP 70) and its mRNA were measured.
AUR increased the intravesical pressure and decreased blood flow, and subsequent catheterization decreased the intravesical pressure and increased blood flow. Edaravone induced a decrease in blood flow in the bladder during the urinary retention and subsequent catheterization compared to the blood flow in the AUR group. Edaravone resulted in protection of the contractile responses to both carbachol and KCl in a dose-dependent manner. The MDA concentration, 8-OHdG content and expressions of HSP-70 and its mRNA in the AUR group were significantly larger than those of the control group. Edaravone markedly suppressed the accumulations of MDA and 8-OHdG in the bladder, and reduced the expressions of HSP 70 and its mRNA.
These results indicate that edaravone reduces the oxidative stress and prevents the bladder dysfunction caused by AUR and subsequent catheterization.
研究自由基清除剂依达拉奉对大鼠膀胱急性尿潴留（AUR）及随后导尿过程中所发生变化的影响。
将8周龄雄性Sprague Dawley大鼠分为四组；一组为诱导尿潴留并随后导尿的AUR组；两组依达拉奉组，分别给予1或10mg/kg体重的依达拉奉60分钟，然后进行相同的尿潴留及随后导尿；一组假手术对照组给予10mg/kg依达拉奉。通过用小夹子夹住大鼠阴茎尿道、进行膀胱造瘘，然后用输液泵输注3mL（0.6mL/分钟）生理盐水来诱导尿潴留。梗阻持续30分钟，然后在研究继续进行时，让膀胱通过留置导管引流60分钟。处死大鼠后，用卡巴胆碱和100mM氯化钾评估膀胱功能，并测量丙二醛（MDA，脂质过氧化标志物）、8-羟基脱氧鸟苷（8-OHdG；氧化性DNA损伤标志物）、热休克蛋白70（HSP 70）及其mRNA的水平。
AUR使膀胱内压升高，血流量降低，随后导尿使膀胱内压降低，血流量增加。与AUR组的血流量相比，依达拉奉在尿潴留及随后导尿期间导致膀胱血流量减少。依达拉奉以剂量依赖性方式保护对卡巴胆碱和氯化钾的收缩反应。AUR组中MDA浓度、8-OHdG含量以及HSP-70及其mRNA的表达明显高于对照组。依达拉奉显著抑制膀胱中MDA和8-OHdG的积累，并降低HSP 70及其mRNA的表达。
这些结果表明，依达拉奉可减轻氧化应激，并预防由AUR及随后导尿引起的膀胱功能障碍。
