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非甾体抗炎药可能对正常肾脏有害:实验性手术模型*

Non steroidal antiinflammatory drugs may be harmful to normal kidneys: experimental surgery model*.

作者信息

Hur E, Duman E, Bozkurt D, Sozmen E, Sen S, Taskin H, Timur O, Kaya So, Duman S

机构信息

Nephrology Dpt, Ege University Medical School, Izmir, Turkey.

出版信息

Hippokratia. 2012 Apr;16(2):160-5.

Abstract

BACKGROUND AND AIM

The exact effect of analgesics on normal kidneys is not known yet. We aimed to evaluate the impression of non steroidal antiinflammatory drugs (NSAID) used post-operatively on kidneys, in rat (tracheotomy) model.

METHODS

Twenty-five non-uremic male wistar albino rats were included. For 18 rats, tracheotomy was performed and divided into two groups. First group, NSAID (diclofenac 10 mg/kg/day intramuscular (im)) (NSAID, n=8); second group isotonic (im)(Control, n=10) were administered for a week. For third group (Histological control,n=7) in order to evaluate normal histology neither surgery nor medication were applied. At the end (7th day), 24 hours urine collected then, blood samples were taken by intracardiac punction and were sacrified. One of the kidneys fixed for histological evaluation, the other was preserved for the measurements of tissue enzyme levels. Lipid peroxidation products and antioxidant enzyme levels were measured both from plasma and renal tissues. Histologically inflammation, regeneration, degeneration assessed semiquatitativelly and immunohistochemical dyes were applied.

RESULTS

Hemoglobin thiobarbituric acid reactive substance level indicating the increase of lipid peroxidation in NSAID group was higher than control group (673±204 vs.373±27nmol/gHb respectively, p>0.05). Superoxide dismutase (one of the antioxidant enzymes responsible for reduction of reactive oxygen substances) and serum nitrate levels were lower in NSAID groups (700±68 vs.1371±164U/gHb and 26±4.4 vs.50.8±6.8 µmol/mL respectively, p<0.05).Although tissue levels were parallel to plasma levels but the difference wasn't significant. In histological assessment degeneration was present only in NSAID group (1.3±0.6 vs.0.0±0, p<0.05). Inflammation were lower than the control group (0.8±0.4 vs.1.2±0.2, p>0.05). Cyclooxygenase-2 expression was disappeared in NSAID group.

CONCLUSIONS

NSAIDs mostly used post-operatively for analgesia, may cause unfavorable effects on kidneys by oxidative stress.

摘要

背景与目的

目前尚不清楚镇痛药对正常肾脏的确切影响。我们旨在评估大鼠(气管切开术)模型中术后使用非甾体抗炎药(NSAID)对肾脏的影响。

方法

纳入25只非尿毒症雄性Wistar白化大鼠。对18只大鼠进行气管切开术并分为两组。第一组,给予NSAID(双氯芬酸10mg/kg/天,肌肉注射)(NSAID组,n = 8);第二组给予等渗液(肌肉注射)(对照组,n = 10),给药一周。第三组(组织学对照组,n = 7),为评估正常组织学,既不进行手术也不给予药物治疗。在实验结束时(第7天),收集24小时尿液,然后通过心脏穿刺采集血样,并处死大鼠。将其中一个肾脏固定用于组织学评估,另一个肾脏保存用于测量组织酶水平。同时测量血浆和肾组织中的脂质过氧化产物和抗氧化酶水平。组织学上,半定量评估炎症、再生、变性情况,并应用免疫组化染料。

结果

NSAID组中表明脂质过氧化增加的血红蛋白硫代巴比妥酸反应性物质水平高于对照组(分别为673±204 vs. 373±27nmol/gHb,p>0.05)。NSAID组中超氧化物歧化酶(负责减少活性氧物质的抗氧化酶之一)和血清硝酸盐水平较低(分别为700±68 vs. 1371±164U/gHb和26±4.4 vs. 50.8±6.8µmol/mL,p<0.05)。虽然组织水平与血浆水平平行,但差异不显著。组织学评估中,变性仅存在于NSAID组(1.3±0.6 vs. 0.0±0,p<0.05)。炎症低于对照组(0.8±0.4 vs. 1.2±0.2,p>0.05)。NSAID组中环氧化酶-2表达消失。

结论

术后常用于镇痛的NSAIDs可能通过氧化应激对肾脏产生不良影响。

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