Expression and significance of neutrophil gelatinase-associated lipocalin in renal interstitial fibrosis in rats

Abstract

To explore the expression and significance of neutrophil gelatinase-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats. A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR), unilateral ureteral obstruction (UUO) and angiotensin-converting enzyme inhibitor (ACEI). The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). And the expressions of NGAL, matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) were observed by immunohistochemistry. (1) The levels of serum NGAL and TNF-α in UUO group obviously increased as compared to those in ACEI and SOR groups (NGAL: (69.2 ± 5.6) vs (41.0 ± 10.4), (10.8 ± 3.8) pg/ml; TNF-α: (116.2 ± 9.2) vs (99.8 ± 14.0), (29.2 ± 5.7) ng/ml; all P < 0.05). (2) The expressions of NGAL, TGF-β1 and MMP-9 in renal tubular epithelial cells of UUO group increased as compared to those in SOR group. The expression of TGF-β1 in ACEI group was apparently less than that in UUO group. The protein levels of NGAL and MMP-9 in ACEI group were obviously lower than those in UUO group within Day 14 post-operation and significantly higher than those in UUO group at Days 21 and 28. (3) In UUO group, the level of NGAL was positively correlated with the serum levels of TNF-α and serum creatinine (r = 0.910, 0.673, P < 0.01). The expression of NGAL had a highly positive correlation with MMP-9 (r = 0.913, P < 0.01) and the index of interstitial damage and the degrees of TGF-β1 at Days 3-7 post-operation(r = 0.937, 0.847, P < 0.01). And the expression of NGAL was negatively correlated with the index of interstitial damage and the degrees of TGF-β1 at Days 14-28 post-operation (r = -0.945, -0.944, P < 0.01). The expression of NGAL significantly increases in UUO modal of rats. And it is closely correlated with MMP-9, TNF-α and TGF-β1. ACEI may influence the biological effects of NGAL by suppressing inflammatory responses, down-regulating the expression of TGF-β1 and regulating the expression and the activity of MMP-9.