大鼠急性肾衰竭后缺血期输注腺嘌呤核苷酸和氯化镁可促进恢复。

Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats.

作者信息

Siegel N J, Glazier W B, Chaudry I H, Gaudio K M, Lytton B, Baue A E, Kashgarian M

出版信息

Kidney Int. 1980 Mar;17(3):338-49. doi: 10.1038/ki.1980.39.

DOI:10.1038/ki.1980.39

Abstract

Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: (1) rats that received no infusion or one of the components of the mixture alone had reduced CIn (355 +/- 40 microliter/min/100 g of body wt vs. 977 +/- 40 control value), decreased RBF (3550 +/- 205 microliter/min/100 g of body wt vs. 5095 +/- 171 control value), elevated FENa (0.65 +/- 0.10% vs. 0.17 +/- 0.04 control value), and diminished UOsm (862 +/- 110 mOsm/kg vs. 1425 +/- 132 control value); (2) rats given dopamine or phenoxybenzamine maintained low CIn (365 +/- 50) despite improved RBF (4678 +/- 222); (3) rats infused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved CIn (594 +/- 44, P < 0.01), increased RBF (4269 +/- 223, P < 0.01); normalized FENa (0.18 +/- 0.07%, P < 0.01), and improved UOsm (1201 +/- 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved CIn despite ischemic periods of 30, 45, and 60- min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and suggest that these agents effectively enhance recovery following an ischemc renal insult.

摘要

尽管在急性肾损伤起始阶段之前或期间进行的一些操作会改变功能损害的程度，但在急性损伤后给予的药物通常无效。在本研究中，在缺血性肾损伤后输注腺嘌呤核苷酸（AMP、ADP或ATP）与氯化镁的混合物。24小时后：（1）未输注或仅单独输注混合物中一种成分的大鼠，其肌酐清除率（CIn）降低（355±40微升/分钟/100克体重，对照组为977±40），肾血流量（RBF）减少（3550±205微升/分钟/100克体重，对照组为5095±171），尿钠排泄分数（FENa）升高（0.65±0.10%，对照组为0.17±0.04），尿渗透压（UOsm）降低（862±110毫渗量/千克，对照组为1425±132）；（2）给予多巴胺或酚苄明的大鼠尽管肾血流量有所改善（4678±222），但肌酐清除率仍维持在低水平（365±50）；（3）输注AMP、ADP或ATP与氯化镁混合物的大鼠肌酐清除率显著改善（594±44，P<0.01），肾血流量增加（4269±223，P<0.01）；尿钠排泄分数恢复正常（0.18±0.07%，P<0.01），尿渗透压改善（1201±106毫渗量/千克，P<0.05）。在未输注或仅输注氯化镁的动物中，超微结构研究显示局灶性细胞坏死以及明显的肾小管细胞和线粒体肿胀，而输注ATP和氯化镁的大鼠超微结构变化较少，细胞形态保存较好。给予ATP和氯化镁治疗的大鼠尽管缺血时间分别为30、45和60分钟，但其肌酐清除率仍有所改善；改善程度与ATP和氯化镁的给药量直接相关。外源性给予的ATP在先前缺血的肾脏中的细胞含量比未缺血的肾脏高2.5倍。数据表明，在急性肾衰竭起始后输注腺嘌呤核苷酸与氯化镁可显著改善肌酐清除率和肾小管功能，并表明这些药物可有效促进缺血性肾损伤后的恢复。