OBJECTIVETo explore the dynamic variation rule of kidney injury makers of molecule 1 (KIM-1), Cystatinc (Cys-C), Blood urea nitrogen (BUN) and Creatinine (Cr) in kidney injury in rats with acute paraquat poisoning.

METHODSHealthy adult rats were randomly divided into control group (normal saline solution) and exposure group (2% paraquat solution 40 mg/kg), and 90 in each group. Six rats in each group were randomly sacrificed at one, one point five, two, three, six, twelve, twenty four, seventy two or one hundred and sixty eight hours after different administration, abdominal aortic blood and the kidney tissue were collected. The concenstrations of kidney injury makers of molecule 1 (KIM-1), cystatinc (Cys-C), blood urea nitrogen (BUN) and creatinine (Cr) were determined by ELASA. The concenstrations of paraquat were determined by HPLC. Pathological changes of kidney tissue that stained by HE were axamined by optical microscopy. The cell apoptosis in kidney tissue were analyzed by TUNEL assay. The ptotein expression of KIM-1 was determined by immunohistochemistry.

RESULTSSerum levels of KIM-1 were significantly increased in exposure group as compared with control group at two, three, six, twelve, twenty four, seventy two or one hundred and sixty eight hours, and the peak level was at twenty four hours, and there was a statistical significance between control group and exposure group (P < 0.01). Serum levels of Cys-C were significantly increased in exposure group as compared with control group at six, twelve, twenty four, seventy two or one hundred and sixty eight hours, the peak level was at twenty four hours, and there was a statistical significance between control group and exposure group (P < 0.01). Serum levels of BUN were significantly increased in exposure group as compared with control group at twelve, twenty four, seventy two or one hundred and sixty eight hours, and the peak level was at seventy two hours, and there was a statistical significance between control group and exposure group (P < 0.01). Compared with control group, there was mild tubular epithelial cells edema in exposure group of three hours, serious epithelial cells edema and few slightly increased glomeruli in exposure group of six hours, severe epithelial cells swelling, tube formation, and interstitial lesions including edema, congestionin and increased inflammatory cell infiltration in exposure group of twelve hours, these pathologic changes gradually reached the peak at twenty four hours, the pathologic injury score was 5.56 ± 0.0349 (P < 0.01), and then the pathological lesion was more palliative. Apoptosis rate of kidney tissue were significantly increased in exposure group as compared with control group at three, six, twelve, twenty four, seventy two or one hundred and sixty eight hours, and the peak level was at twenty four hours, and there was a statistical significance between control group and exposure group (P < 0.01). The immunohistochemical assay indicated that KIM-1 of control group were weakly positive expressed in tubular epithelial cell membrane, but the positive expression of KIM-1 were slightly increased in exposure group of two hours, the.immunohistochemistry score was 5.47 ± 0.1033 (P < 0.05), the positive expression of KIM-1 were gradually increased in exposure group of three, six and twelve hours, it reached peak at twenty four hours, the.immunohistochemistry score was 11.73 ± 0.4676 (P < 0.01), then the positive expression of KIM-1 decreased, but there was still positive expression at one hundred and sixty eight hours.

CONCLUSIONSerum levels of KIM-1 and Cys-C were significantly increased in the kidney injury in rats with acute paraquat poisoning in early stage, earlier than the changes of BUN and Cr. KIM-1 had relation with apoptosis rate. Cys-C had relation with pathological lesion changes.

Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Cystatin C ; blood ; Immunohistochemistry ; Kidney ; drug effects ; pathology ; Membrane Glycoproteins ; blood ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley