title: Neutrophil gelatinase-associated lipocalin (NGAL) may play a protective role against rats ischemia/reperfusion renal injury via inhibiting tubular epithelial cell apoptosis.
abstract: We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) on rats ischemia/reperfusion (I/R) renal injury. Eighteen Sprague-Dawley male rats were randomly divided into three groups. Control group (n = 6) suffered left unilateral nephrectomy, I/R + NS (normal saline) (n = 6) and I/R + NGAL (n = 6) group were subjected to 45 min right renal ischemia/24 h reperfusion after left unilateral nephrectomy. Serum creatinine (Scr) and blood urea nitrogen (Bun) were measured on automatic biochemistry analyzer; kidney sections were stained with hematoxylin-eosin; terminal dUTP nick-labeling method was used to examine the apoptosis of tubular epithelial cells; Cleaved caspase-3 and Bax protein expression were detected by immunohistochemistry and Western Blot; real-time polymerase chain reaction was used to detect the expression of Bax mRNA. Rats with NGAL displayed an attenuated renal damage and a decreased number of tubular epithelial cell apoptosis compared to the I/R + NS group (Scr 63.400 ± 11.908 vs. 121.857 ± 17.151 μmol/L, Bun 14.840 ± 2.868 vs. 28.557 ± 6.434 mmol/L, apoptosis cell number 7.800 ± 1.924 vs. 15.400 ± 3.049/high power field (HPF), p < 0.05), the values were lower in the control group (24.000 ± 3.829 μmol/L, 5.814 ± 1.961 mmol/L, 1.800 ± 0.837/HPF, p < 0.05) compared to two groups above; NGAL-treated rats showed down-regulated Cleaved caspase-3 protein (0.284 ± 0.066 vs. 0.409 ± 0.073, p < 0.05), Bax protein (0.346 ± 0.055 vs. 0.443 ± 0.041, p < 0.05), Bax mRNA (1.423 ± 0.187 vs. 2.550 ± 0.217, p < 0.05) compared to I/R + NS group, but the values were higher in both of the two groups than those in the control group (Cleaved caspase-3 protein 0.104 ± 0.029, Bax protein 0.155 ± 0.027, Bax mRNA 1.000 ± 0.000, p < 0.05). We supposed that exogenous NGAL can inhibit the activation of caspase-3, reduce the expression of Bax, and thus reduce renal tubular cell apoptosis and protect renal function in I/R injury rats.
authors.affiliation: Department of Nephrology, Shanghai First People's Hospital Affiliated to Jiaotong University, Shanghai, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: An
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zang
authors.forename: Weijie
authors.initials: W
authors.lastname: Yuan
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhuge
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000008:administration & dosage*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; D012313:RNA; D053148:Caspase 3