Shoskes D A
Department of Surgery, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California 90509, USA.
Transplantation. 1998 Jul 27;66(2):147-52. doi: 10.1097/00007890-199807270-00001.
Nonimmune renal injury plays an important role in acute and chronic rejection by triggering an injury response through cytokine and chemokine release. Bioflavonoids are agents with potential immunosuppressive and renoprotective properties. We studied the effects of quercetin and curcumin, two bioflavonoids, on ischemia-reperfusion in the rat.
Rats underwent 30 min of left renal pedicle occlusion with simultaneous right nephrectomy and were pretreated with quercetin or curcumin. Serial serum creatinine was measured, and renal expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), and allograft inflammatory factor (AIF) was quantified by polymerase chain reaction.
Pretreatment with quercetin or curcumin resulted in preservation of histological integrity, with a decrease in tubular damage and interstitial inflammation. On day 2 after ischemia-reperfusion, quercetin pretreatment decreased the mean serum creatinine level from 6.5+/-1.4 to 3.3+/-0.5 mg/dl (P=0.06). On day 7, the creatinine level for control animals was 7.5+/-1.5 mg/dl, which was significantly decreased by pretreatment with quercetin, curcumin, or both together (creatinine levels: 1.6+/-1.3, 1.8+/-0.2, and 2.0+/-0.4 mg/dl, respectively; all P<0.05 vs. untreated). By semiquantitative polymerase chain reaction, RANTES, MCP-1, and AIF were detected at high levels in kidneys on day 2 but not in normal kidneys. Pretreatment with quercetin or curcumin strongly attenuated this expression.
Quercetin and curcumin reduce ischemia-reperfusion injury and its inflammatory sequelae. The bioflavonoids hold promise as agents that can reduce immune and nonimmune renal injury, the key risk factors in chronic graft loss.
非免疫性肾损伤通过细胞因子和趋化因子的释放引发损伤反应，在急性和慢性排斥反应中起重要作用。生物类黄酮是具有潜在免疫抑制和肾脏保护特性的药物。我们研究了两种生物类黄酮槲皮素和姜黄素对大鼠缺血再灌注的影响。
大鼠接受30分钟的左肾蒂闭塞并同时切除右肾，并分别用槲皮素或姜黄素进行预处理。测定系列血清肌酐水平，并通过聚合酶链反应对激活后正常T细胞表达和分泌的趋化因子（RANTES）、单核细胞趋化蛋白-1（MCP-1）和移植炎症因子（AIF）的肾表达进行定量。
用槲皮素或姜黄素预处理可保持组织学完整性，减少肾小管损伤和间质炎症。缺血再灌注后第2天，槲皮素预处理使平均血清肌酐水平从6.5±1.4降至3.3±0.5mg/dl（P=0.06）。第7天，对照动物的肌酐水平为7.5±1.5mg/dl，用槲皮素、姜黄素或两者联合预处理可使其显著降低（肌酐水平分别为：1.6±1.3、1.8±0.2和2.0±0.4mg/dl；与未处理组相比，P均<0.05）。通过半定量聚合酶链反应，第2天在肾脏中检测到高水平的RANTES、MCP-1和AIF，但在正常肾脏中未检测到。用槲皮素或姜黄素预处理可强烈减弱这种表达。
槲皮素和姜黄素可减轻缺血再灌注损伤及其炎症后遗症。生物类黄酮有望成为可减少免疫性和非免疫性肾损伤的药物，而免疫性和非免疫性肾损伤是慢性移植物丢失的关键危险因素。
