Effects of olprinone, a phosphodiesterase III inhibitor, on ischemic acute renal failure
Effects of olprinone, a phosphodiesterase III inhibitor, on ischemic acute renal failure
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DOI：
10.1111/j.1442-2042.2007.01689.x
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发表时间：
2007-03-01
影响因子：
2.6
通讯作者：
Matsuo, Seiichi
中科院分区：
文献类型：
--
作者：
Anas, Chabouk;Ozaki, Takenori;Matsuo, Seiichi
目的：肾缺血再灌注损伤(IRI)是肾移植中不可避免的问题，也是目前肾移植面临的主要问题之一。本研究旨在探讨磷酸二酯酶III抑制剂奥普利酮对大鼠肾脏IRI的影响。奥普利酮有两种不同的给药方式：持续的全身给药和肾脏的暂时性局部给药。对照组大鼠注射生理盐水。用放大内窥镜测量再灌注后23h的肾血流速度。然后，采集血样，取肾脏标本进行组织学研究。为了探讨其作用机制，我们用人近端肾小管上皮细胞(HK-2)与肿瘤坏死因子(TNF)-α、奥普利酮或生理盐水共同孵育，进行体外实验，并测定培养上清液中白细胞介素8(IL-8)的含量。结果：生理盐水组肾小管上皮细胞的血流速度较正常肾组织明显减慢。奥普利酮治疗组大鼠肾微循环血流量明显增加，肾小管损伤减轻，巨噬细胞浸润减轻，肾功能明显改善。奥普利酮可抑制HK-2与肿瘤坏死因子α孵育所致的IL-8水平升高。结论：奥普利酮局部和全身应用均具有肾脏保护作用。提示奥普利酮可用于供肾、受者的肾移植，甚至可用于急性肾功能衰竭的治疗。
Objective: 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.Methods: 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.Results: 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.Conclusions: 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.