Study on the mechanism of action of NGAL in renal anemia on iron metabolism and erythrocyte maturation

Objective To explore the potential mechanism and main influencing factors of neutrophil gelatinase-associated lipocalin(NGAL) in iron metabolism and erythrocyte maturation of renal anemia, and finding new therapeutic targets for renal anemia. Methods Forty-five SD rats were divided into control group and observation group. The observation group used adenine to establish a renal anemia model. The control group was intragastrically administered with equal volume of distilled water. After 6 weeks of modeling, Hb, BUN, SCr, TAST, Fer, EPO, NGAL, TNF-α, IL-1, IL-6 were measured. RT-PCR was used to detect the expression of NGAL mRNA and EPOR mRNA in renal tissue, bone marrow, and the expression of NGAL protein and EPOR protein in renal tissue and bone marrow by Western blot. And assessing the association between indicators. Results Compared with the control group, the Hb of the model group was significantly decreased(P<0.01), the TAST, EPO decreased(P<0.05), the Fer,IL-1,IL-6,TNF-α increased(P<0.05), and the SCr, BUN and serum NGAL were significantly increased(P<0.01). The NGAL mRNA was significantly increased(P<0.01) and the EPOR mRNA was decreased(P<0.05) in the kidneys of the model group. The NGAL mRNA in the bone marrow of the model group was lower than that in the normal group(P>0.05), and the EPOR mRNA was decreased(P<0.05). The levels of NGAL protein in the kidneys were increased(P<0.05), and the levels of EPOR protein were decreased(P<0.05). Compared with the control group, the levels of NGAL protein in the bone marrow of the model group were decreased(P<0.05), and the level of EPOR protein was slightly decreased(P<0.05).>0.05). Serum NGAL was positively correlated with SCr, Fer, kidney NGAL, IL-1, IL-6 and TNF-α, and negatively correlated with Hb, TAST, and bone marrow NGAL. Kidney NGAL was positively correlated with SCr, Fer, serum NGAL, IL-1, IL-6 and TNF-α and negative with Hb, TAST, bone marrow NGAL, serum EPOR, and bone marrow EPOR. Correlation; bone marrow NGAL was positively correlated with Hb, serum EPOR, and renal EPOR, and negatively correlated with SCr, Fer, serum NGAL, kidney NGAL,IL-1,IL-6 and TNF-α. Conclusions NGAL may pass an inflammatory response in renal anemia, affecting not only iron metabolism but also red blood cell maturation, which may be an alternative therapeutic target for improving secondary anemia such as renal anemia.