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磷酸二酯酶4抑制剂咯利普兰对大鼠急性上行性肾盂肾炎模型氧化肾损伤的预防作用

Preventive effect of rolipram, a phosphodiesterase 4 enzyme inhibitor, on oxidative renal injury in acute ascending pyelonephritis model in rats.

作者信息

Görür Sadik, Celik Sefa, Hakverdi Sibel, Aslantaş Ozkan, Erdoğan Suat, Aydin Muhsin, Ocak Sabahattin, Namik Kiper Ahmet

机构信息

Department of Urology, Mustafa Kemal University Faculty of Medicine, Antioch-Hatay, Turkey.

出版信息

Urology. 2008 Oct;72(4):743-8. doi: 10.1016/j.urology.2008.04.013. Epub 2008 Jun 13.

DOI:10.1016/j.urology.2008.04.013
PMID:18554698
Abstract

OBJECTIVES

To evaluate the effects of rolipram, a phosphodiesterase 4 enzyme inhibitor, on Escherichia coli-induced renal oxidative damage in an acute pyelonephritis (PYN) rat model.

METHODS

A total of 35 male Wistar albino rats were randomly divided into 7 groups (n = 5) as follows: control (uninfected), PYN 24 hours, PYN 48 hours, PYN 72 hours, PYN + rolipram 24 hours, PYN + rolipram 48 hours, and PYN + rolipram 72 hours. Ascending PYN was induced in the study groups by E. coli inoculation into the bladder, and the urethras were then occluded by collodium for 4 hours. Rolipram injections (1 mg/kg) were started before bacterial inoculation and repeated at 24-hour intervals in the PYN + rolipram groups until death. The rats were killed at the indicated times. Malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were determined in kidney homogenates. Histopathologic examinations were also performed.

RESULTS

Tissue malondialdehyde and nitric oxide levels and superoxide dismutase and catalase activities were significantly increased in the kidneys from the PYN groups. However, rolipram administration reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. The histopathologic examinations demonstrated that rolipram treatment reduced the inflammation grade in the kidney specimens.

CONCLUSIONS

The results of our study have shown that rolipram has a protective effect on renal tissue from E. coli-induced oxidative injury. Therefore, phosphodiesterase 4 inhibitors might be a novel therapeutic option for the prevention and/or management of acute PYN.

摘要

目的

在急性肾盂肾炎(PYN)大鼠模型中,评估磷酸二酯酶4抑制剂咯利普兰对大肠杆菌诱导的肾脏氧化损伤的影响。

方法

总共35只雄性Wistar白化大鼠被随机分为7组(n = 5),如下:对照组(未感染)、PYN 24小时组、PYN 48小时组、PYN 72小时组、PYN + 咯利普兰24小时组、PYN + 咯利普兰48小时组和PYN + 咯利普兰72小时组。通过将大肠杆菌接种到膀胱中在研究组中诱导上行性PYN,然后用火棉胶封闭尿道4小时。在细菌接种前开始注射咯利普兰(1 mg/kg),并在PYN + 咯利普兰组中每隔24小时重复注射,直至大鼠死亡。在指定时间处死大鼠。测定肾匀浆中的丙二醛和一氧化氮水平以及超氧化物歧化酶和过氧化氢酶活性。还进行了组织病理学检查。

结果

PYN组大鼠肾脏中的组织丙二醛和一氧化氮水平以及超氧化物歧化酶和过氧化氢酶活性显著增加。然而,给予咯利普兰可降低肾脏丙二醛和一氧化氮水平,并增强超氧化物歧化酶和过氧化氢酶活性。组织病理学检查表明,咯利普兰治疗降低了肾脏标本中的炎症等级。

结论

我们的研究结果表明,咯利普兰对大肠杆菌诱导的肾脏氧化损伤的肾组织具有保护作用。因此,磷酸二酯酶4抑制剂可能是预防和/或治疗急性PYN的一种新的治疗选择。

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