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


CONCLUSIONS
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.
Cao
Ju
J
Renal Division, Departments of Medicine, First Hospital, Peking University, Beijing 100034, China.
Yang
Xue-dong
XD
Wang
Xiao-ying
XY
Qu
Lei
L
Liu
Gang
G
Li
Xiao-mei
XM
D000818:Animals; D034341:Aristolochic Acids / Q000009:adverse effects*; D005839:Gentamicins / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D034341:Aristolochic Acids; D005839:Gentamicins; C000228:aristolochic acid I