title: [Characteristics of changes in urinary NGAL, KIM-1 and IL-18 in Phytolaccae Radix-induced renal injury in rats and significance of combined detection].
abstract: OBJECTIVE
  To explore the characteristics of changes in neutrophil gelatinase-associated lipocalcin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in Phytolaccae Radix-induced kidney injury in rats and the significance of the combined detection.
  
  
  METHODS
  Wistar rats were divided into three groups: high and low dose (crude drug 40, 20 g x kg(-1) x d(-1)) Phytolaccae Radix decoction groups and the control group, and orally administrated with distilled water or equal volume of Phytolaccae Radix decoction for 35 consecutive days. Their blood and urine samples were collected on day 7, 14, 21, 28, 35,42. The anatomical analysis was conducted for each group. The contents of serum total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CR) and urinary TP and ALB were detected-by means of biochemical analyzer. The concentrations of urinary NGAL, KIM-1 and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of renal pathology were observed by light or electron microscopy. The curve areas of various serum or urine indexes and the combined detection were compared by receiver operating characteristic curve (ROC curve).
  
  
  RESULTS
  Rats were given Phytolaccae Radix decoction at the doses of 40, 20 g crude drug/kg daily for 35 consecutive days to induce kidney injury characterized by the degeneration of renal tubular epithelial cell and protein cast. The injury was partially reversible during the recovery period. Compared with the control group, the content of serum BUN, CR and urinary TP in each dose group mostly showed a downward trend. On day 21, the content of urinary ALB obviously increased till the end of administration. The contents of urinary NGAL, KIM-1 and IL-18 began increasing on day 7. Since day 14, high and low dose groups showed significant difference (P<0.01). The high dose group even showed notable changes during the recovery period. According to ROC analysis, the curve areas of NGAL, KIM-1 and IL-18 were 0.846, 0.837 and 0.863 (P <0.01), respectively, much higher than that of BUN and CR. The area of the combined detection was up to 0.947.
  
  
  CONCLUSIONS
  Urinary NGAL, IL-18 and KIM-1 could forecast and indicate the occurrence and development of renal injury to some degree, and show higher sensitivity and site specificity. The combined detection could further improve the test efficiency.
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. liyifei725@yahoo.com.cn
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Li
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Xu
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Yao
authors.forename: Ruo-Min
authors.initials: RM
authors.lastname: Jin
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000009:adverse effects*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000209:Acute-Phase Proteins; D015815:Cell Adhesion Molecules; D004365:Drugs, Chinese Herbal; D020382:Interleukin-18; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat