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[马兜铃酸和庆大霉素所致急性肾小管坏死大鼠模型肾内氧合的差异变化]

[Differential changes of intrarenal oxygenation in rat models of acute tubular necrosis caused by aristolochic acid and gentamicin].

作者信息

Cao Ju, Yang Xue-dong, Wang Xiao-ying, Qu Lei, Liu Gang, Li Xiao-mei

机构信息

Renal Division, Departments of Medicine, First Hospital, Peking University, Beijing 100034, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 May 4;90(17):1208-12.

Abstract

OBJECTIVES

To investigate the characteristics of renal oxygenation status in aristolochic acids I (AA-I) induced ATN rat model by method of blood oxygenation level-dependent MRI (BOLD-MRI) and compare it with ATN model caused by gentamicin.

METHODS

28 male Wistar rats were randomly divided into control, AAN and GM groups, which were subcutaneously injected with normal saline, AA-I (25 mg x kg(-1)x d(-1)) or GM (200 mg x kg(-1)x d(-1)) respectively for 4 days. Intrarenal oxygenation was measured by BOLD-MRI at 4(th) day and 7(th) day. Renal histopathological changes and renal function were also observed at day 7.

RESULTS

Serum level of creatinine and urinary NAG were obviously elevated at day 7 in AAN and gentamicin group. Diffuse tubular necrosis confined to the margin of renal cortex and medulla without edema or infiltration of inflammation cells was the main pathological finding in AAN group. BOLD-MRI revealed that renal medullar R2() was elevated significantly at both day 4 [(50.6 +/- 15.6)/s vs (35.6 +/- 4.3)/s, P < 0.01] and day 7 [(58.4 +/- 14.8)/s vs (37.8 +/- 3.6)/s, P < 0.01] in AAN group when compared to control, showing opposite changes to GM group whose R2() was decreased at the same time. In addition, the renal cortical R2(*) in AAN group was also higher than that of control [(40.3 +/- 14.7)/s vs (28.7 +/- 3.2)/s, P < 0.05] at day 7, showing opposite changes to GM group.

CONCLUSION

Intrarenal hypoxia exists in acute AAN rats, which initiates in the medulla following an involvement in renal cortex. The phenomenon of persistent low level of intrarenal oxygenation is different from change of GM-induced ATN, which may contribute to the progression of renal interstitial fibrosis in AAN.

摘要

目的

采用血氧水平依赖性功能磁共振成像(BOLD-MRI)方法研究马兜铃酸I(AA-I)诱导的急性肾小管坏死(ATN)大鼠模型的肾脏氧合状态特征,并与庆大霉素所致ATN模型进行比较。

方法

将28只雄性Wistar大鼠随机分为对照组、AA-I组和庆大霉素组,分别皮下注射生理盐水、AA-I(25mg·kg⁻¹·d⁻¹)或庆大霉素(200mg·kg⁻¹·d⁻¹),连续4天。于第4天和第7天采用BOLD-MRI测量肾脏氧合情况。第7天观察肾脏组织病理学变化及肾功能。

结果

AA-I组和庆大霉素组第7天血清肌酐水平和尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)明显升高。AA-I组主要病理表现为局限于肾皮质和髓质交界处的弥漫性肾小管坏死,无水肿或炎症细胞浸润。BOLD-MRI显示,与对照组相比,AA-I组第4天[(50.6±15.6)/s对(35.6±4.3)/s,P<0.01]和第7天[(58.4±14.8)/s对(37.8±3.6)/s,P<0.01]肾髓质R2显著升高,与同期R2降低的庆大霉素组变化相反。此外,AA-I组第7天肾皮质R2*也高于对照组[(40.3±14.7)/s对(28.7±3.2)/s,P<0.05],与庆大霉素组变化相反。

结论

急性AA-I大鼠存在肾脏内缺氧,始于髓质,随后累及肾皮质。肾脏内氧合持续处于低水平的现象与庆大霉素诱导的ATN变化不同,这可能是AA-I导致肾间质纤维化进展的原因。

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