POSTISCHEMIC RENAL INJURY IS MEDIATED BY NEUTROPHILS AND LEUKOTRIENES
POSTISCHEMIC RENAL INJURY IS MEDIATED BY NEUTROPHILS AND LEUKOTRIENES
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DOI：
10.1152/ajprenal.1989.256.5.f794
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发表时间：
1989-05-01
影响因子：
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通讯作者：
HECHTMAN, HB
中科院分区：
文献类型：
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作者：
KLAUSNER, JM;PATERSON, IS;HECHTMAN, HB
嗜中性粒细胞在心肌和骨骼肌缺血再灌注损伤中起中枢介质的作用。本研究测试了这些细胞因子和趋化剂白三烯（LTB4）是否在缺血性肾衰竭中起作用。麻醉大鼠左肾蒂夹持45分钟。再灌注5 min后，大鼠LTB4水平升高至1.42 ng/ml (P < 0.05)；血栓素（Tx）B2为2840 pg/ml，高于假对照组的503 pg/ml (P < 0.05)；再灌注1 min时肾动脉血流量为预夹紧值的67%，假手术组为111% （P < 0.05）。24h时肌酐水平为4.6 mg/dl (P < 0.05)；组织学显示急性肾小管坏死（ATN）。兔抗血清（n = 8）导致再灌注时中性粒细胞耗竭，LTB4和TxB2水平分别降低1.04 ng/ml和1,043 pg/ml (P < 0.05)；肾血流量增加174% (P < 0.05)；肌酐降低1.8 mg/dl (P < 0.05)；有限的ATN。二乙胺嘧啶预处理可抑制LTB4和TxB2升高（P < 0.05），增加肾血流量（P < 0.05），使肌酐降至1.7 mg/dl (P < 0.05)，降低ATN。这些数据表明，中性粒细胞和LTB4在缺血诱导的Tx合成和介导缺血后肾损伤中发挥作用。
Neutophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P < 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P < 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P < 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P < 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1,043 pg/ml (P < 0.05); increased renal blood flow of 174% (P < 0.05); reduced creatinine levels of 1.8 mg/dl (P < 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P < 0.05), increased renal blood flow (P < 0.05), minimized creatinine increase to 1.7 mg/dl (P < 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.