Preventive effect Of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats
Preventive effect Of L-carnosine on ischemia/reperfusion-induced acute renal failure in rats
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DOI：
10.1016/s0014-2999(03)02079-x
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发表时间：
2003-08-08
影响因子：
5
通讯作者：
Matsumura, Y
中科院分区：
文献类型：
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作者：
Fujii, T;Takaoka, M;Matsumura, Y
我们研究了l-肌肽（β -丙烯酰- l-组氨酸）对大鼠缺血性急性肾功能衰竭的影响。对侧肾切除术后2周，阻断左肾动静脉45分钟后再灌注诱导缺血性急性肾功能衰竭。急性肾功能衰竭大鼠在再灌注后第1天肾功能明显下降。左旋卡莫苷剂量依赖性缺血前处理（1,10马克杯/千克，静脉注射）可减轻缺血/再灌注引起的肾功能障碍。未经治疗的急性肾功能衰竭大鼠肾脏组织病理学检查显示严重的肾损害，每次给予l -肌肽预处理可显著抑制肾损害。急性肾功能衰竭大鼠肾静脉血浆去甲肾上腺素浓度在再灌注后2 min内显著升高，随后迅速下降。10 mg /kg剂量的左旋甘油三酯可显著降低已升高的去甲肾上腺素水平。另一方面，虽然在再灌注后5分钟给予高剂量左旋卡莫苷有改善再灌注后肾功能的倾向，但与缺血前治疗相比，改善程度较轻。上述结果表明，左旋卡莫苷可阻止缺血/再灌注引起的肾损伤的发生，并可抑制再灌注后肾脏中去甲肾上腺素的释放。因此，左旋卡莫苷对缺血性急性肾功能衰竭的预防作用可能是通过抑制缺血/再灌注引起的肾交感神经活动增强。(C) 2003 Elsevier B.V.版权所有
We investigated the effect of L-carnosine (beta-alanyl-L-histidine) on ischemic acute renal failure in rats. Ischemic acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in untreated acute renal failure rats markedly decreased at I day after reperfusion. Pre-ischemic treatment with L-camosine dose-dependently (1, 10 mug/kg, i.v.) attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of untreated acute renal failure rats revealed severe renal damage, which was significantly suppressed by pre-treatment With L-carnosine, at each dose given. In untreated acute renal failure rats, norepinephrine concentrations in renal venous plasma remarkably increased within 2 min after reperfusion and thereafter rapidly decreased. Pre-ischemic treatment With L-camosine at a dose of 10 mug/kg significantly depressed the elevated norepinephrine level. On the other hand, although the higher dose of L-camosine given 5 min after reperfusion tended to ameliorate the renal dysfunction after reperfusion, the improvement was moderate compared with those seen in pre-ischemic treatment. These results indicate that L-camosine prevents the development of ischemia/reperfusion-induced renal injury, and the effect is accompanied by suppression of the enhanced norepinephrine release in the kidney immediately after reperfusion. Thus, the preventing effect Of L-camosine on ischemic acute renal failure is probably through the suppression of enhanced renal sympathetic nerve activity induced by ischemia/reperfusion. (C) 2003 Elsevier B.V. All rights reserved.