Pathogenesis of anemia in chronic aristolochic acid nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To study the pathogenesis of anemia in chronic aristolochic acid nephmpathy(CAAN) rats. Methods The hemoglobin(Hb)values of sixty-two male SD rats were assayed to determine its normal range.Among them,24 rats with normal Hb value were randomly divided into 2 groupsmodel group (MG)in which rats received the extract of Aristololochia manshuriensis Kom (AmK) by gavage,and control group (CG) received tap water only by gavage.Body weisht(BW),Hb,24 h urinary protein excretion(UP)and creatinine clearance (Ccr)of 6 rats in each group were measured before administration and at the end of the 8th week, respeetively.then these rats were sacrificed.The relative area of renal interstitial fibrosis was measured by microscopy.The mRNA expression of erythropoietin (EPO)in kidney tissue Was determined by real-time RT-PCR;protein expression of type I collagen(Coll),aminopeptidase P (APP),hypoxia indHeible factor let and 2α(HIF-1α and HIF-2α)in kidney tissue Was examined by immunohistochemistry staining. Results Hb values of normal rats presented normal distribution. The normal Hb was (155.9±16.5) g/L. Rat anemia was diagnosed when Hb was below 123.6 g/L. There was no difference in all the examination results between CG and MG before administration (P>0.05). Compared with CG, the Hb and Cer in MG were significantly decreased [(121.66±15.68) g/L vs (169.00±12.89) g/L, (0.63±0.13) ml/min vs (1.27±0.18) ml/min, P< 0.01], and the UP in MG was significantly increased at the end of the 8th week [(27.04±9.40) mg/d vs (6.11±0.84) mg/d, P<0.01]; the relative areas of fibrosis and Col l in renal interstitium of MG were significantly enlarged [(12.89±2.33)% vs (0.55±0.10)%, (13.92±2.92)% vs (1.32±0.84)%, P<0.01]; the protein expression of APP and the mRNA expression of EPO in the kidney tissue of MG were significantly down-regulated [(0.55±0.23)% vs (3.77±1.06)%, 0.005±0.001 vs 0.032±0.013, P<0.01]; the protein expression of HIF-lα and HIF-2α in the kidney tissue of MG was significantly up-regulated (2.55±0.16 vs 1.12±0.46, 2.33±0.33 vs 1.15±0.27, P<0.01), at the end of the 8th week. Conclusions The pathogenesis of anemia in CAAN may be due to the decreased production of EPO caused by the destruction of peritubular capillary. The compensatory up-regulation of HIF-lα and HIF-2α expression can not prevent the anemia development.