Activition of serum secretory phospholipase A2 in rats with acute kidney injury induced by aristolochic acid / 中华肾脏病杂志

ABSTRACT

Objective To investigate whether the activation of secretory prophospholipase A2 (sPLA2) plays the role in the pathophysiological mechanism of acute aristolochic acid nephropathy (AAN) in rats. Methods Wistar rats were randomly divided into two groups. Model group received decocted Aristolochia Manshuriensis Kom 30 g·kg-1d-1 by gavage for 7 days following tap water in same way for additional 7 days. Control group received only tap water by garage at parallel time. The renal pathological changes were observed at the 4th, 8th and 14th day. The injury of renal tubules and interstitium was observed under light microscope following a semi-quantity grade. The level of Scr was measured to evaluate glomerular function. Urinary N-acetyl-beta-glucosaminidase (NAG) was tested as renal tubular injury marker. The activity of sPLA2 in serum was detected by manifesting the color of thiols in the substrate. The protein expression of renal cortex and medulla COX-2 was analyzed by Western blot. The metabolic products of pretaglandins (PC, s) including 6-kcto-PGF1α and TXB2 in the plasma and urine were assayed by radioimmunoassay. The ratio of 6-keto-PGF1α/TXB2 was calculated. Results After Aristolochia administration, the tubulointerstitial injury and Scr increased in AA rats and reached the peak at the 8th day, the tubulointerstitial injury index(8.14±2.55 vs 1.50±0.71, P<0.05) and Scr[(0.24±0.10) vs (0.19±0.02) μmol/g, P<0.05] increased significantly in AA rats compared with control group. The activity of sPLA2 (μmol ·min-1·mg-1) in AA group elevated by 1.3-fold compared to control group at 8th day (133.15±17.05 vs 101.3±16.07, P<0.05), while theexpression of COX-2 in renal cortex increased (1.16±0.36 vs 0.69±0.28, P<0.05) with no change in renal medulla. Even though the levels of serum 6-keto-PGF1α and TXB2 did not change obviously in both AA and control group, but urinary levels of 6-keto-PGF1α and TXB2 increased by 2-fold and 3-fold in AA group compared to control group, respectively (all P<0.05), while the ratio of 6-keto-PGF1α/TXB2 decreased significantly (207.53±17.52 vs 296.64±51.31, P<0.05). All of above changes recovered to the control level at the 14th day except the tubulointerstitial injury index. Conclusion Serum sPLA2 is activated in the rots with acute kidney injury induced by aristolochic acid, which accompanied by up-regulated expression of COX-2 in renal cotex and increased the metabolic products of vasoconstrictive PG s in urine. These changes may participate the mechanism of renal peritubular ischemia in AAN.