Li W J, Bergman S M, Holmes R P, Strandhoy J W, Handa R K, McCullough D L
Department of Urology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.
J Urol. 1992 Feb;147(2):519-22. doi: 10.1016/s0022-5347(17)37292-0.
Tetrodotoxin has been reported to cause prolonged systemic hypotension without resultant ischemic damage. We tested its ability to protect the kidney during 60 minutes of warm ischemia in uninephrectomized rats. Protection was observed when tetrodotoxin was given intravenously at two microgram./kg. and four microgram./kg. as assessed by serial plasma blood urea nitrogen and creatinine measurements over two weeks. Tetrodotoxin was protective when given immediately before or immediately after the ischemic period. The renal protection of tetrodotoxin was not due to its effects on renal nerves as renal denervation did not protect the kidney from the ischemic damage. The renal protective effects of four microgram. tetrodotoxin/kg. were similar to those of four mg. captopril/kg. but the combination of the two was paradoxically without effect. We tested whether tetrodotoxin and captopril chemically antagonized each other, but in the presence of tetrodotoxin, captopril was still a potent inhibitor of the conversion of angiotensin I to angiotensin II. These results indicate that tetrodotoxin could be useful in elucidating the sequence of events associated with ischemic-reperfusion renal injury and in identifying ways of preserving renal function during renal surgery.
据报道，河豚毒素可导致持续性全身性低血压，但不会造成缺血性损伤。我们测试了其在单侧肾切除大鼠60分钟热缺血期间保护肾脏的能力。通过连续两周测量血浆血尿素氮和肌酐评估，当以2微克/千克和4微克/千克静脉注射河豚毒素时，观察到了保护作用。在缺血期之前或之后立即给予河豚毒素具有保护作用。河豚毒素的肾脏保护作用并非因其对肾神经的影响，因为去肾神经支配并不能保护肾脏免受缺血性损伤。4微克河豚毒素/千克的肾脏保护作用与4毫克卡托普利/千克相似，但两者联合使用却出乎意料地没有效果。我们测试了河豚毒素和卡托普利是否会发生化学拮抗作用，但在存在河豚毒素的情况下，卡托普利仍是血管紧张素I转化为血管紧张素II的有效抑制剂。这些结果表明，河豚毒素可能有助于阐明与缺血再灌注肾损伤相关的事件序列，并有助于确定在肾脏手术期间保护肾功能的方法。
