Anas Chabouk, Ozaki Takenori, Maruyama Shoichi, Yamamoto Tokunori, Zu Gotoh Momoka, Ono Yoshinari, Matsuo Seiichi
Departments of Urology and Nephrology, Nagoya University Graduate School of Medicine, 65 Tsusumaicho, Showaku, Nagoya, Aichi, Japan.
Int J Urol. 2007 Mar;14(3):219-25. doi: 10.1111/j.1442-2042.2007.01689.x.
Renal ischemic reperfusion injury (IRI) is unavoidable and is still one of the major problems in renal transplantation. The aim of this study was to investigate the effects of olprinone, a phosphodiesterase III inhibitor, on renal IRI.
After a right nephrectomy, renal IRI was induced in rats. Olprinone was given in two different ways: sustained systemic administration and transient local administration to the kidney. Control rats were treated with saline. Using a magnifying endoscope, the renal blood flow speed was measured at 23 h after reperfusion. Then, blood samples were collected, and kidney specimens were taken for histological study. In order to study the mechanism, we performed in vitro experiments, using human proximal renal tubular cells (HK-2) incubated with tumor necrosis factor (TNF)-alpha along with olprinone or saline, and interleukin (IL)-8 was measured in the culture supernatant.
In the saline group, the blood flow speed (BFS) was greatly reduced compared to that in normal kidneys. In both olprinone-treated groups, BFS of the renal microcirculation significantly increased, tubular damage and macrophage infiltration attenuated, and renal function greatly improved. Olprinone inhibited the increase in the IL-8 levels resulting from the incubation of HK-2 with TNF-alpha.
Our study successfully demonstrates that olprinone has renoprotective properties when applied locally as well as systemically. The results suggest that olprinone might be clinically useful in renal transplantation for the donor kidney, the recipient, and even in treating acute renal failure.
肾缺血再灌注损伤（IRI）在肾移植中不可避免，仍是主要问题之一。本研究旨在探讨磷酸二酯酶III抑制剂奥普力农对肾IRI的影响。
大鼠行右肾切除术后诱导肾IRI。奥普力农以两种不同方式给药：持续全身给药和肾脏短暂局部给药。对照组大鼠用生理盐水治疗。使用放大内镜在再灌注后23小时测量肾血流速度。然后采集血样，并取肾脏标本进行组织学研究。为研究机制，我们进行体外实验，将人近端肾小管细胞（HK - 2）与肿瘤坏死因子（TNF）-α一起孵育，并加入奥普力农或生理盐水，然后测量培养上清液中的白细胞介素（IL）- 8。
与正常肾脏相比，生理盐水组的血流速度（BFS）大幅降低。在两个奥普力农治疗组中，肾微循环的BFS均显著增加，肾小管损伤和巨噬细胞浸润减轻，肾功能显著改善。奥普力农抑制了HK - 2与TNF -α孵育导致的IL - 8水平升高。
我们的研究成功证明，奥普力农局部和全身应用均具有肾保护特性。结果表明，奥普力农在肾移植中对供肾、受者甚至治疗急性肾衰竭可能具有临床应用价值。
