[Expression of kidney injury molecule-1 in renal ischemic postconditioning and its protective effect against renal ischemia-reperfusion injury in rats].
OBJECTIVE
To investigate whether the protective mechanism of ischemic postconditioning (IPO) against renal ischemia reperfusion injury (IRI) is related  to the expression of kidney injury molecule-1 (Kim-1), and whether Kim-1 can reflect the protective effect of ischemic postconditioning as a sensitive  biomarker in rats so as to find early and effective indicators to use IPO in clinical research of urology in future.


METHODS
Eighty-five male SD rats (240-300 g) were randomly divided into three groups (IRI: n=30; IPO: n=30; sham operation group: n=25). After the right nephrectomy through median abdominal  incision to make the solitary kidney model, the left renal artery was separated from the renal pedicle. In IRI group, the left renal artery was blocked for 45  min before reperfusion. In IPO group, six cycles of 10 s reperfusion-10 s reocclusion of the left kidney were performed after 45 min ischemia. The blood  samples and the kidney cortex tissues were taken at the time points of 6 h, 12 h, 24 h, 48 h and 72 h after reperfusion, with 5 rats for each time point. The  plasma samples were obtained for urea and creatinine detection. A modified quantitative RT-PCR was used to quantitate the Kim-1 mRNA expression  of renal tissue. Five rats were chosen from groups IRI and IPO respectively to obtain the urine samples of each rat, 0 h, 6 h, 12 h, 24 h, 48 h, and 72 h after  reperfusion. The Kim-1 levels of urine were detected by ELISA. Pathological examinations were performed to check the differences between the three  groups.


RESULTS
Urine tests and RT-PCR showed that, in IRI and IPO groups, Kim-1 and its mRNA levels began to rise after 6 h of reperfusion and  reached the peak at 24 h synchronously. Urine Kim-1 levels in IRI group were significantly higher than those of the IPO group at 6 h, 12 h, 24 h, 72 h  (P<0.05). The Kim-1 mRNAs in IPO group were lower than those in IRI group at the time points of 6 h, 12 h, 24 h, and 48 h (P<0.05), and the levels  decreased more rapidly after 24 h. BUN and Cr significantly increased at 12 h, which were later than the Kim-1 and Kim-1 mRNA. The BUN and Cr levels  in IRI group were higher than those in IPO group after 24 h (P<0.05). The pathological examination showed that there was less epithelial injury in IPO group.


CONCLUSIONS
Ischemic postconditioning can attenuate the renal ischemia reperfusion injury and downregulate the expression of Kim-1 and Kim-1  mRNA. Kim-1, as a biomarker and protective factor of acute kidney injury (AKI), can sensitively reflect the renal protective effect by ischemic  postconditioning.
Department of Urology, Peking University Third Hospital, Beijing, China.
Xiang
X
Ji
Lu-lin
LL
Ma
Jian
J
Lu
Shu-dong
SD
Zhang
Yi
Y
Huang
Xiao-fei
XF
Hou
Xin
X
Ma
D000818:Animals; D015415:Biomarkers / Q000652:urine; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D057775:Ischemic Postconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; C110936:Havcr1 protein, rat