Camerano Gabriela Verónica, Bustuoabad Oscar David, Meiss Roberto Pablo, Gómez Sonia Alejandra, Fernández Gabriela Cristina, Isturiz Martín Amadeo, Palermo Marina Sandra, Dran Graciela Isabel
Sección Medicina Experimental, Academia Nacional de Medicina, Buenos Aires, Argentina.
Pediatr Nephrol. 2006 Aug;21(8):1082-92. doi: 10.1007/s00467-006-0115-5. Epub 2006 May 16.
Uninephrectomy (Unx) is followed by the compensatory renal growth (CRG) of the remaining kidney. Previous evidence has shown that during CRG, renal tissue is resistant to a variety of pathologies. We tested the hypothesis that the functional changes that take place during CRG could attenuate Shiga toxin (Stx) toxicity in a mouse model of Stx2-induced hemolytic uremic syndrome (HUS). The participation of nitric oxide (NO) was analyzed. After CRG induction with Unx, mice were exposed to a lethal dose of Stx2, and the degree of renal damage and mortality was measured. Stx2 effects on the growth, renal blood flow (RBF) and NO synthase (NOS) intrarenal expression in the remaining kidney were then studied. The induction of CRG strongly prevented Stx2-mediated mortality and renal damage. Administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) during CRG partially impaired the protection. Both Stx2 and L-NAME interfered with the hypertrophic and hyperplastic responses to Unx, as well as with the increase in RBF. In intact mice, Stx2 decreased renal perfusion, inhibited endothelial NOS basal expression and enhanced inducible NOS expression; all of these effects were attenuated by prior Unx. It is concluded that during CRG mice are highly protected against Stx2 toxicity and lethality. The protective capacity of CRG could be related to the enhancement of renal perfusion and preservation of eNOS renal expression, counterbalancing two major pathogenic mechanisms of Stx2.
单侧肾切除术后，剩余肾脏会出现代偿性肾生长（CRG）。先前的证据表明，在CRG过程中，肾组织对多种病理状态具有抗性。我们在志贺毒素2（Stx2）诱导的溶血尿毒综合征（HUS）小鼠模型中，检验了CRG期间发生的功能变化可减轻志贺毒素（Stx）毒性的假说。分析了一氧化氮（NO）的参与情况。在用单侧肾切除诱导CRG后，将小鼠暴露于致死剂量的Stx2，并测量肾损伤程度和死亡率。然后研究Stx2对剩余肾脏生长、肾血流量（RBF）和肾内一氧化氮合酶（NOS）表达的影响。CRG的诱导强烈预防了Stx2介导的死亡率和肾损伤。在CRG期间给予NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）会部分削弱这种保护作用。Stx2和L-NAME均干扰了对单侧肾切除的肥大和增生反应，以及RBF的增加。在完整小鼠中，Stx2降低了肾灌注，抑制了内皮型NOS的基础表达并增强了诱导型NOS的表达；所有这些效应在预先进行单侧肾切除后均减弱。结论是，在CRG期间，小鼠对Stx2毒性和致死性具有高度保护作用。CRG的保护能力可能与肾灌注的增强和内皮型NOS肾表达的保留有关，从而抵消了Stx2的两个主要致病机制。
