Nitric Oxide Kinetics and Early Intervention Acute Renal Allograft Rejection in Rat.

最近的研究表明，在心脏、肝脏、胰腺和肾脏移植后的急性排斥反应中，一氧化氮合酶(NO)合酶，尤其是诱导型一氧化氮合酶(I-NOS)被大量诱导。此外，移植物中的组织和细胞损伤已被证明是由NO的代谢物过氧亚硝酸阴离子(ONOO-)介导的，ONOO-是一种有效的生物氧化剂。另一方面，在人肾移植的慢性排斥反应中，ONOO-参与了自由基清除剂锰超氧化物歧化酶(MnSOD)的硝化和失活。然而，NO、I-NOS、ONOO-和MnSOD在急性排斥反应中的详细关系仍不清楚。我们用大鼠模型获得了以下结果。在大鼠移植肾急性排斥反应中，血清NO水平显著升高，同时组织i-NOS活性增强，共同导致移植物损伤。氨基胍(AG)是一种有效的i-NOS抑制剂，可抑制血清NO水平的升高，同时减轻组织损伤和肾功能损害。此外，在同种异体移植组中，与同种异体移植组相比，MnSOD活性显著降低，同时灭活的酪氨酸硝化MnSOD活性增加，从而导致ONOO-产物(硝基酪氨酸)在肾小管中积聚，这是移植物损伤的原因。

Recent studies have shown that nitric oxide(NO) synthases, particularly inducible nitric oxide synthase(i-NOS), are massively induced in acute rejection episodes following heart, liver, pancreas and kidney allotransplantation. Furthemore, tissue and cellular injury in grafts has been demonstrated to be mediated by peroxynitrite anion(ONOO-), a metabolite of NO as well as a potent biological oxidant. On the other hand, in chronic rejection of human renal allografts, ONOO-has been implicated in nitration and inactivation of manganese-superoxide dismutase(MnSOD), a radical scavenger. However, a detailed relationship between NO, i-NOS, ONOO-and MnSOD in acute rejection episodes remains elusive. The following results weve abtained using rat models. In rat renal allograft acute rejection, markedly increased levels of serum NO were observed, along with enhanced tissue i-NOS activity, together resulting in graft injury. The administration of Aminoguanidine(AG), a potent i-NOS inhibitor, suppressed the increase in serum NO levels, with concomitant mitigation of tissue injury and renal function impair ment. Furthermore, in the allograft group, MnSOD activity was significantly decreased compared to the isograft group, in parallel with increased inactivated tyrosine-nitrated MnSOD, thus leading to accumulation of ONOO-products(nitrotyrosine) in tubules accounting for graft injuries.