氨磷汀对大鼠肾缺血再灌注的肾保护作用。

Renoprotective potency of amifostine in rat renal ischaemia-reperfusion.

机构信息

Laboratoire de Chirurgie Expérimentale, UPRES EA 1602, Université Paris-Sud 11, APHP Hôpital Bicêtre, Faculté de Médecine, Le Kremlin-Bicêtre, France.

出版信息

Nephrol Dial Transplant. 2010 Dec;25(12):3845-51. doi: 10.1093/ndt/gfq314. Epub 2010 Jun 4.

DOI:10.1093/ndt/gfq314

PMID:20525975

Abstract

PURPOSE

Kidneys from haemodynamically unstable donors may suffer from renal ischaemia-reperfusion (RIR) injury. RIR is associated with reactive oxygen species production that induces inflammation and activates the arachidonic acid (AA) pathway which converts AA into prostaglandin E(2). Amifostine was investigated for its renoprotective potential in RIR.

MATERIALS AND METHODS

The effect of amifostine (25 mg/kg = 910 mg/m(2)) on the COX pathway, enzymatic antioxidant activity, the lipid peroxidation marker MDA, serum creatinine and apoptosis was determined in rats. Kidneys were subjected to 45 min of ischaemia and 1 or 24 h of reperfusion. Control groups (sham: coeliotomy, no ischaemia; r1: 45 min ischaemia/1 h reperfusion; r2: 45 min ischaemia/24 h reperfusion) were administered physiological saline intraperitoneally, and treated groups (E1: 45 min ischaemia/1 h reperfusion; E2: 45 min ischaemia/24 h reperfusion) received amifostine 30 min before reperfusion.

RESULTS

Serum creatinine increased in non-treated control rats: r1 vs sham (1.6-fold; P <0.007), r2 vs sham (2-fold; P <0.007). Amifostine decreased serum creatinine levels in treated rats: E1 vs r1 (8%; P <0.0025), E2 vs r2 (44%; P <0.0025). Amifostine reduced acute tubular necrosis (25%) 24 h after reperfusion: E1 vs r1 (P <0.004), E2 vs r2 (P <0.03) and reduced COX-2 and microsomal prostaglandin E synthase expression: E1 vs r1 (P <0.03), E2 vs r2 (P <0.02). Amifostine decreased MDA (P <0.04) and reduced caspase-3 expression but did not alter enzymatic antioxidant activity after RIR.

CONCLUSIONS

Amifostine decreased the degree and severity of tubular damage after reperfusion, probably by scavenging oxygen free radicals and attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis.

摘要

目的

血流动力学不稳定供体的肾脏可能会遭受肾缺血再灌注（RIR）损伤。RIR 与活性氧（ROS）的产生有关，ROS 诱导炎症并激活花生四烯酸（AA）途径，将 AA 转化为前列腺素 E（2）。研究了氨磷汀在 RIR 中的肾保护作用。

材料和方法

在大鼠中，用氨磷汀（25mg/kg=910mg/m2）确定 COX 途径、酶抗氧化活性、脂质过氧化标志物 MDA、血清肌酐和细胞凋亡的影响。肾脏经历 45 分钟缺血和 1 或 24 小时再灌注。对照组（假手术：剖腹术，无缺血；r1：45 分钟缺血/1 小时再灌注；r2：45 分钟缺血/24 小时再灌注）接受腹腔内生理盐水注射，治疗组（E1：45 分钟缺血/1 小时再灌注；E2：45 分钟缺血/24 小时再灌注）在再灌注前 30 分钟接受氨磷汀。

结果

非治疗对照大鼠的血清肌酐升高：r1 与 sham（1.6 倍；P <0.007），r2 与 sham（2 倍；P <0.007）。氨磷汀降低了治疗大鼠的血清肌酐水平：E1 与 r1（8%；P <0.0025），E2 与 r2（44%；P <0.0025）。氨磷汀减少了再灌注后 24 小时的急性肾小管坏死（25%）：E1 与 r1（P <0.004），E2 与 r2（P <0.03），并降低了 COX-2 和微粒体前列腺素 E 合酶的表达：E1 与 r1（P <0.03），E2 与 r2（P <0.02）。氨磷汀降低 MDA（P <0.04），并减少 caspase-3 表达，但在 RIR 后并未改变酶抗氧化活性。