Guanosine supplementation reduces apoptosis and protects renal function in the setting of ischemic injury
Guanosine supplementation reduces apoptosis and protects renal function in the setting of ischemic injury
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DOI：
10.1172/jci13018
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发表时间：
2001-11-01
影响因子：
15.9
通讯作者：
Dagher, PC
中科院分区：
文献类型：
--
作者：
Kelly, KJ;Plotkin, Z;Dagher, PC
肾脏缺血性损伤的部分特征是核苷酸耗尽和肾小管细胞以坏死或凋亡的形式死亡。最近，我们将缺氧诱导的肾细胞凋亡与GTP的耗竭联系起来。因此，我们推测，增强体内GTP的补充可能通过减少缺血后小管的凋亡来保护功能。雄性C57黑鼠(“I”组)夹闭双侧肾动脉32min造成缺血，然后给予生理盐水(“NS”)或鸟苷(“G”)。再灌流1h后，NS/I组小鼠肾脏GTP水平降至假手术组的近一半，而G/I组小鼠肾脏GTP水平几乎没有变化。肾小管损伤的形态学检查显示，两组间无显著差异。但与NS/I组相比，G/I组大鼠延髓内肾小管细胞的凋亡数明显减少。在24小时，与G/I组相比，NS/I组的肌酐显著升高。我们的结论是，鸟苷通过补充GTP储备和防止肾小管细胞凋亡来保护肾缺血损伤。
Ischemic injury to the kidney is characterized in part by nucleotide depletion and tubular cell death in the form of necrosis or apoptosis. Recently, we linked anoxia-induced apoptosis in renal cell cultures specifically to the depletion of GTP. We therefore hypothesized that enhancing GTP repletion in vivo might protect function by reducing apoptosis in postischemic tubules. Male C57 black mice (the "I" group of animals) underwent bilateral renal artery clamp for 32 minutes to induce ischemia and then received either normal saline ("NS") or guanosine ("G"). After I hour of reperfusion, renal GTP levels in NS/I were reduced to nearly half of those in sham operated mice, whereas these levels were nearly unchanged in G/I mice. Morphologic examination of tubular injury revealed no significant differences between the two groups. However, there was a significant reduction in the number of apoptotic tubular cells in the medulla in the G/I group as compared with the NS/I group. At 24 hours, creatinine was significantly elevated in the NS/I group, compared to the G/I group. We conclude that guanosine protects against renal ischemic injury by replenishing GTP stores and preventing tubular apoptosis.