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肾上腺髓质素对大鼠造影剂诱导的肾病的保护作用。

Protective effect of adrenomedullin on contrast induced nephropathy in rats.

作者信息

Inal Salih, Koc Eyüp, Ulusal-Okyay Gülay, Pasaoglu Ozge T, Isik-Gönül Ipek, Oz-Oyar Eser, Pasaoglu Hatice, Güz Galip

出版信息

Nefrologia. 2014 Nov 17;34(6):724-31. doi: 10.3265/Nefrologia.pre2014.Sep.12405. Epub 2014 Oct 20.

Abstract

BACKGROUND AND AIMS

Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN.

METHODS

Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining.

RESULTS

Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers.

CONCLUSION

This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.

摘要

背景与目的

对比剂诱导的肾病(CIN)发病率不断上升,其中肾血管收缩和髓质缺氧是重要机制。治疗方法非常有限,因此人们对推进预防策略有着浓厚兴趣。肾上腺髓质素是一种相对较新的肽,具有抗氧化、血管活性和血管舒张特性。我们旨在研究肾上腺髓质素是否可能对实验性CIN的发展具有预防作用。

方法

将24只Wistar白化大鼠随机分为四组,每组6只;分别为对照组(C)、肾上腺髓质素组(A)、造影剂组(CM)和肾上腺髓质素加造影剂组(ACM)。在72小时内,所有大鼠从第1天到第4天禁水。然后进行化学物质的静脉注射。向A组和ACM组给予剂量为12μg/kg的肾上腺髓质素。向CM组和ACM组注射单剂量高渗造影剂泛影葡胺(德国先灵公司的Urografin 76%),剂量为10mL/kg。在第1天和第6天采集血样进行肾功能测试以及检测包括肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和白细胞介素-18在内的炎症标志物。处死后,用苏木精-伊红染色检查肾脏组织学。

结果

与CM组相比,ACM组第6天的血清胱抑素-C水平显著降低(p<0.05)。此外,ACM组的每日蛋白质排泄率、每日尿量的绝对变化和肌酐清除率值均显著低于CM组(p<0.05)。在组织病理学评估中,就肾小管损伤程度和髓质充血评分而言,ACM组的评分略优于CM组;然而,与炎症标志物所示情况一样,差异未达到显著水平。

结论

本研究表明肾上腺髓质素对实验性CIN模型中恶化的肾功能测试有有益影响。肾上腺髓质素可能是预防CIN的候选药物。然而,需要进一步研究以更清楚地阐明这一问题。

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