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依达拉奉对大鼠睾丸缺血再灌注损伤的保护作用。

Protective effect of edaravone, a free-radical scavenger, on ischaemia-reperfusion injury in the rat testis.

机构信息

Department of Pathophysiological and Therapeutic Science, Tottori University Yonago, Japan.

出版信息

BJU Int. 2010 Mar;105(6):870-6. doi: 10.1111/j.1464-410X.2009.08798.x. Epub 2009 Aug 19.

Abstract

OBJECTIVE

To investigate the effect of edaravone, a radical scavenger, on ischaemia-reperfusion (I-R) injury in the testes.

MATERIALS AND METHODS

Eight-week-old male Sprague-Dawley rats were allocated to one of four groups: a no-drug group subjected to induction of 30-min of ischaemia and 60-min reperfusion; two drug groups administered edaravone at 1 or 10 mg/kg intraperitoneal and then subjected to 30-min ischaemia and 60-min reperfusion; and a sham-operated control group administered edaravone at 10 mg/kg intraperitoneal. To induce testicular I-R, the right testis was exposed outside of the body and the testicular artery was clamped with a small clip for 30 min. Blood flow and nitric oxide (NO) release were monitored in real time simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. After death the tissue levels of NO(2)-NO(3) (a marker of NO production), malondialdehyde (a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage), myeloperoxidase (a marker of neutrophil infiltration), and heat-shock protein 70 (HSP 70) and its mRNA were measured. The testicular tissue was also analysed histologically.

RESULTS

Clamping the testicular artery resulted in a decrease of blood flow to 0-5% of the basal level measured before clamping. NO release was increased during clamping and gradually recovered to the basal level on removing the clip. Interestingly, the peak of NO release in rats of the no-drug group occurred at the start of reperfusion, while that in the high-dose drug group occurred several minutes later. The levels of NO(2)-NO(3), malondialdehyde, 8-hydroxydeoxyguanosine, myeloperoxidase and HSP 70 and its mRNA, and histological variables, were significantly greater in the no-drug I-R group than in the control, and these variables were ameliorated by treatment with edaravone.

CONCLUSION

These results indicate that edaravone reduces the oxidative stress and prevents the testicular damage induced by I-R.

摘要

目的

研究自由基清除剂依达拉奉对缺血再灌注(I-R)损伤睾丸的影响。

材料和方法

将 8 周龄雄性 Sprague-Dawley 大鼠分为四组:无药物组,接受 30 分钟缺血和 60 分钟再灌注;两组药物组分别给予依达拉奉 1 或 10mg/kg 腹腔注射,然后进行 30 分钟缺血和 60 分钟再灌注;假手术对照组给予依达拉奉 10mg/kg 腹腔注射。为了诱导睾丸 I-R,将右侧睾丸暴露在体外,用小夹子夹住睾丸动脉 30 分钟。同时用激光多普勒血流计和一氧化氮(NO)选择性电极实时监测血流和 NO 释放。处死大鼠后,测量组织中 NO(2)-NO(3)(NO 生成的标志物)、丙二醛(脂质过氧化的标志物)、8-羟基脱氧鸟苷(氧化 DNA 损伤的标志物)、髓过氧化物酶(中性粒细胞浸润的标志物)和热休克蛋白 70(HSP 70)及其 mRNA 的水平。还对睾丸组织进行了组织学分析。

结果

夹闭睾丸动脉导致血流降至夹闭前基础水平的 0-5%。夹闭期间 NO 释放增加,并在去除夹子后逐渐恢复到基础水平。有趣的是,无药物 I-R 组大鼠的 NO 释放峰值出现在再灌注开始时,而高剂量药物组大鼠的峰值出现在几分钟后。无药物 I-R 组的 NO(2)-NO(3)、丙二醛、8-羟基脱氧鸟苷、髓过氧化物酶和 HSP 70 及其 mRNA 水平以及组织学变量均显著高于对照组,依达拉奉治疗可改善这些变量。

结论

这些结果表明,依达拉奉可减轻氧化应激并预防 I-R 引起的睾丸损伤。

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