Szakaly Peter, Kiss Peter, Lubics Andrea, Magyarlaki Tamas, Tamas Andrea, Racz Boglarka, Lengvari Istvan, Toth Gabor, Reglodi Dora
Department of Surgery, University of Pecs, Pecs, Hungary.
J Mol Neurosci. 2008 Nov;36(1-3):89-96. doi: 10.1007/s12031-008-9064-8. Epub 2008 May 14.
Pituitary adenylate cyclase activating polypeptide (PACAP) occurs and exerts a variety of biological functions in the nervous system and in the peripheral organs, including the urinary system. PACAP has protective effects against myeloma kidney injury and renal ischemia. Ischemia/reperfusion injury of the kidney is a major clinical problem, and based on the protective effects of PACAP in cerebral and cardiomyocyte ischemia, the aim of the present study was to evaluate the effects of a single intravenous PACAP injection on the survival and renal morphology after varying times of ischemia. Rats were subjected to renal artery clamping for 15, 30, 45, 60, or 75 min followed by reperfusion. PACAP (100 microg) was administered intravenously before arterial clamping. We found that a 15- or 30-min renal ischemia led to no renal dysfunction, and the kidneys showed normal appearance with no difference between PACAP- and saline-treated groups. Control rats with 45 min of ischemia had increased premature death rate and showed multifocal acute tubular atrophy, while a 60-min ischemia led to death of all control animals within a few days displaying severe, multifocal Grade II tubular atrophy. In contrast, all PACAP-treated animals survived with subtle morphological changes after the 45-min ischemia. After the 60-min ischemia, death rate was significantly lower in PACAP-treated rats compared to controls, and animals showed subtle focal tubular alteration. A 75-min ischemia was not performable in controls because of deaths before the termination of ischemia. PACAP-treated rats survived longer, but they also died after 5-10 days exhibiting severe focal tubular atrophy. In summary, our results clearly show that PACAP is able to prolong the renal ischemic time, decrease mortality, and attenuate tubular degeneration after renal ischemia.
垂体腺苷酸环化酶激活多肽（PACAP）存在于神经系统和包括泌尿系统在内的外周器官中，并发挥多种生物学功能。PACAP对骨髓瘤肾损伤和肾缺血具有保护作用。肾脏缺血/再灌注损伤是一个主要的临床问题，基于PACAP对脑和心肌细胞缺血的保护作用，本研究的目的是评估单次静脉注射PACAP对不同缺血时间后肾脏存活和肾脏形态的影响。将大鼠的肾动脉夹闭15、30、45、60或75分钟，然后再灌注。在动脉夹闭前静脉注射PACAP（100微克）。我们发现，15或30分钟的肾缺血未导致肾功能障碍，肾脏外观正常，PACAP治疗组和生理盐水治疗组之间无差异。缺血45分钟的对照大鼠过早死亡发生率增加，出现多灶性急性肾小管萎缩，而缺血60分钟导致所有对照动物在几天内死亡，表现为严重的多灶性II级肾小管萎缩。相比之下，所有接受PACAP治疗的动物在缺血45分钟后存活下来，形态学变化轻微。缺血60分钟后，与对照组相比，接受PACAP治疗的大鼠死亡率显著降低，动物表现出轻微的局灶性肾小管改变。由于在缺血结束前死亡，对照组无法进行75分钟的缺血实验。接受PACAP治疗的大鼠存活时间更长，但它们也在5-10天后死亡，表现为严重的局灶性肾小管萎缩。总之，我们的结果清楚地表明，PACAP能够延长肾脏缺血时间，降低死亡率，并减轻肾脏缺血后的肾小管变性。
