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磷酸二酯酶-4 特异性抑制剂罗利普兰对大鼠肾缺血再灌注损伤的保护作用。

Protective effects of phosphodiesterase-4-specific inhibitor rolipram on acute ischemia-reperfusion injury in rat kidney.

机构信息

Department of Urology, Faculty of Medicine, University of Çukurova, Adana, Turkey.

出版信息

Urology. 2012 Dec;80(6):1390.e1-6. doi: 10.1016/j.urology.2012.07.028. Epub 2012 Sep 23.

DOI:10.1016/j.urology.2012.07.028
PMID:23010343
Abstract

OBJECTIVE

To investigate the effect of Rolipram, a phosphodiesterase-4-inhibitor, on renal ischemia-reperfusion injury (IRI) in rats.

METHODS

Thirty rats were divided into 5 different groups of 6 rats. Nothing was done to the control group. In the second group, the renal pedicle was clamped for 30 minutes. In the third group, 1 mg/kg of Rolipram was given by intraperitoneal injection 30 minutes before clamping. The fourth group received the same injection when the clamp was placed, as did the fifth group 30 minutes after the clamp was opened. Clamping time was set at 30 minutes. Twenty-four hours later, nephrectomy was performed in all the groups. Half of each kidney was examined histopathologically. Levels of biochemical agents, such as malondialdehyde, superoxide dismutase, and catalase, were measured in the other half.

RESULTS

The malondialdehyde (MDA) levels significantly decreased and reached control levels in the group in which Rolipram was administered 30 minutes after reperfusion (P = .07). The catalase and superoxide dismutase activities obtained from renal homogentisates of the ischemia groups were evaluated; there were striking increases in tissue levels of these 2 enzymes in the groups in which Rolipram was administered during ischemia and 30 minutes after ischemia (P < .001). Histopathologically, there was no significant difference in inflammation between the Rolipram-administrated groups compared with group 1 (control) and group 2 (IRI). Tubular necrosis and apoptosis was significantly lower in group 5 than the other groups, except group 1 (P < .001).

CONCLUSION

We suggest that in surgical procedures that can lead to renal IRI, the administration of Rolipram can decrease oxidative renal tissue damage and the severe deterioration of renal function.

摘要

目的

研究磷酸二酯酶-4 抑制剂罗利普兰(Rolipram)对大鼠肾缺血再灌注损伤(IRI)的影响。

方法

30 只大鼠分为 5 组,每组 6 只。对照组不做任何处理。第二组夹闭肾蒂 30 分钟。第三组在夹闭前 30 分钟腹腔内注射 1mg/kg 的罗利普兰。第四组和第五组在夹闭时和夹闭后 30 分钟给予相同的注射。夹闭时间设定为 30 分钟。所有组 24 小时后行肾切除术。一半的肾脏进行组织病理学检查。另一半测量生化剂(如丙二醛、超氧化物歧化酶和过氧化氢酶)的水平。

结果

再灌注 30 分钟后给予罗利普兰的组丙二醛(MDA)水平显著降低并接近对照水平(P=.07)。评估缺血组肾匀浆中过氧化氢酶和超氧化物歧化酶的活性;在给予罗利普兰的缺血组和缺血后 30 分钟组,组织水平的这两种酶显著增加(P<.001)。组织病理学上,与对照组 1(IRI)和组 2(IRI)相比,给予罗利普兰的组炎症程度无显著差异。与其他组相比,除组 1 外,组 5 的肾小管坏死和凋亡明显更低(P<.001)。

结论

我们认为,在可能导致肾 IRI 的手术过程中,给予罗利普兰可以减少氧化肾组织损伤和肾功能的严重恶化。

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