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由尿路致病性大肠杆菌引起的急性肾损伤的实验模型

Experimental model for acute kidney injury caused by uropathogenic Escherichia coli.

作者信息

Skowron Beata, Baranowska Agnieszka, Kaszuba-Zwoińska Jolanta, Więcek Grażyna, Malska-Woźniak Anna, Heczko Piotr, Strus Magdalena

机构信息

Department of Pathophysiology, Jagiellonian University Medical College, Krakow, Poland.

Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland.

出版信息

Postepy Hig Med Dosw (Online). 2017 Jun 19;71(0):520-529. doi: 10.5604/01.3001.0010.3833.

Abstract

INTRODUCTION

Acute kidney injury (AKI) is the rapid deterioration of renal function, diagnosed on the basis of an increase in serum creatinine and abnormal urinary parameters. AKI is associated with increased risk of mortality or chronic kidney disease (CKD). The aim of the study was to develop an experimental model for AKI resulting from Escherichia coli-induced pyelonephritis. E. coli was isolated from a patient with clinical symptoms of urinary tract infection (UTI).

MATERIAL/METHODS: The study included three groups of female Wistar rats (groups 1, 2 and 3), in which pyelonephritis was induced by transurethral inoculation with highly virulent E. coli (105, 107 and 109 cfu/ml, respectively). Urine and blood samples for analysis were obtained prior to the inoculation (day 0), as well as 7, 14 and 21 days thereafter.

RESULTS

Aside from a microbiological examination of urine samples, daily urine output, serum creatinine (CreaS), creatinine clearance (CrCl), interleukin 6 (IL-6), fractional excretion of sodium (FENa) and fractional excretion of urea (FEUrea) were determined. A histopathological examination of kidney and urinary bladder specimens was conducted as well. While UTI-related pyelonephritis developed irrespective of E. coli inoculum size, AKI was observed only following transurethral administration of E. coli at the intermediate and high dose, i.e. 107 and 109 cfu/ml, respectively (group 2 and 3).

DISCUSSION

An increase in CreaS and abnormal diuresis were accompanied by changes in parameters specific for various forms of AKI, i.e. FENa and FEUrea. Based on these changes, administration of E. coli at 107 cfu/ml was demonstrated to induce renal AKI, whereas inoculation with 109 cfu/ml seemed to cause not only ascending pyelonephritis, but perhaps also bacteremia and urosepsis (prerenal component of AKI).

摘要

引言

急性肾损伤(AKI)是指肾功能迅速恶化,依据血清肌酐升高和异常尿液参数进行诊断。AKI与死亡率增加或慢性肾脏病(CKD)相关。本研究的目的是建立一种由大肠杆菌引起的肾盂肾炎导致的AKI实验模型。大肠杆菌从一名有尿路感染(UTI)临床症状的患者中分离得到。

材料/方法:本研究包括三组雌性Wistar大鼠(第1、2和3组),通过经尿道接种高毒力大肠杆菌(分别为105、107和109 cfu/ml)诱导肾盂肾炎。在接种前(第0天)以及接种后7、14和21天采集尿液和血液样本进行分析。

结果

除了对尿液样本进行微生物学检查外,还测定了每日尿量、血清肌酐(CreaS)、肌酐清除率(CrCl)、白细胞介素6(IL-6)、钠分数排泄率(FENa)和尿素分数排泄率(FEUrea)。同时对肾脏和膀胱标本进行了组织病理学检查。虽然无论大肠杆菌接种量大小,均会发生与UTI相关的肾盂肾炎,但仅在经尿道给予中、高剂量大肠杆菌,即分别为107和109 cfu/ml时(第2组和第3组)观察到AKI。

讨论

CreaS升高和利尿异常伴随着各种形式AKI的特异性参数变化,即FENa和FEUrea。基于这些变化,证明以107 cfu/ml的剂量给予大肠杆菌可诱导肾性AKI,而接种109 cfu/ml似乎不仅会导致上行性肾盂肾炎,还可能导致菌血症和尿脓毒症(AKI的肾前成分)。

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