Geranylgeranylacetone attenuates renal ischemia reperfusion injury / 中华肾脏病杂志

ABSTRACT

Objective To explore the protective effects of geranylgeranylacetone (GGA) on acute renal failure tats induced by isehemia reperfusion (IR) and the possible mechanism. Methods GGA (400 mg/kg) was administered to induce overexpression of heat shock protein 72 (HSP72) in the kidney of Sprague-Dawley (SD) rats. IR model was generated by temporary clamping the left renal artery for 45 minutes followed by right nephrectomy and 24 h reperfusion. A sham-operated group was used as normal control. 24 h after reperfnsion, rats were sacrificed. Blood was collected for measurement of serum creatinine (Scr) and blood urea nitrogen ( BUN ). Paraffin-embedded sections of the kidney were stained with PAS. Histological changes due to tubular damage were quantitated as tubular damage score. TUNEL assay was used to detect the apoptosis, and Western-blot was used to detect the expression of XIAP. Results After renal IR, the increased level of BUN and Scr, the tubular injury and the apoptosis of renal tubular epithelial cells were observed (P＜0.01). At the same time, the decreased level of XIAP was observed (P＜ 0.01). Compared with the control groups, the level of HSP72 expression was up-regulated in oral administration of GGA group (P＜0.05). The expression levels of BUN and serum creatinine were significantly decreased after IR injury in pre-conditioned rats with over-expression of HSP72 (P＜ 0.01 ). Kidney morphology was better preserved in GGA group. Rats with over-expression of HSP72 also revealed reduction of apoptotic cells by TUNEL stain and XIAP degradation by Western blot (P＜0.05). Conclusion GGA attenuates renal IR injury at least in part through inhibiting tubular cell apoptosis by decreasing XAIP degradation and restoring XIAP protein level.