Barbosa P S F, Havt A, Facó P E G, Sousa T M, Bezerra I S A M, Fonteles M C, Toyama M H, Marangoni S, Novello J C, Monteiro H S A
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel Nunes de Melo 1127, 60430-270 Fortaleza, CE, Brazil.
Toxicon. 2002 Oct;40(10):1427-35. doi: 10.1016/s0041-0101(02)00156-3.
Acute renal failure is one the most common systemic complications after snakebite, however, its pathogenesis remains obscure. In this study we evaluated the renal effects of Bothrops moojeni venom and its myotoxins (Bmtx-I and BmtxII) in rat isolated perfused kidneys. The myotoxins were purified by ion-exchange chromatography and reverse phase HPLC. The whole venom (10 microg/ml) and myotoxins (5 microg/ml) were added to the perfusion system 30 min after the beginning of each perfusion. The renal effects were compared to a control group perfused with modified Krebs-Henseleit solution alone. B. moojeni venom decreased the perfusion pressure (PP), renal vascular resistance (RVR), and the percent sodium, potassium and chloride tubular transport (%TNa(+), %TK(+), %TCl(-)). In contrast, the venom increased the urinary flow (UF), glomerular filtration rate (GFR), and the sodium, potassium and chloride excretion (ENa(+), EK(+), ECl(-)). The renal effects of myotoxin I was very similar to those of the whole venom, but there was an increase rather than a decrease in the PP and RVR. Myotoxin II had no effect on renal physiology, except for a transient decrease in %TK(+). In conclusion, B. moojeni venom caused intense alterations in renal physiology, including a drop in vascular resistance associated with diuresis, natriuresis and kaliuresis. Bmtx-I had an opposite effect when compared to whole venom, showed in the parameters of PP and RVR. Bmtx-II had a mild effect in %TK(+). The apparent inability of Bmtx-II to induce the renal effect similarly to Bmtx-I should be explained by the absence in the Bmtx-II of the C-terminal lysine rich region.
急性肾衰竭是蛇咬伤后最常见的全身并发症之一,然而其发病机制仍不清楚。在本研究中,我们评估了矛头蝮蛇毒及其肌毒素(Bmtx-I和BmtxII)对大鼠离体灌注肾脏的影响。肌毒素通过离子交换色谱和反相高效液相色谱进行纯化。在每次灌注开始30分钟后,将全毒液(10微克/毫升)和肌毒素(5微克/毫升)加入灌注系统。将肾脏效应与仅用改良的克雷布斯-亨泽莱特溶液灌注的对照组进行比较。矛头蝮蛇毒降低了灌注压(PP)、肾血管阻力(RVR)以及钠、钾和氯的肾小管转运百分比(%TNa(+)、%TK(+)、%TCl(-))。相反,毒液增加了尿流(UF)、肾小球滤过率(GFR)以及钠、钾和氯的排泄(ENa(+)、EK(+)、ECl(-))。肌毒素I对肾脏的影响与全毒液非常相似,但PP和RVR是增加而不是降低。肌毒素II除了使%TK(+)短暂降低外,对肾脏生理没有影响。总之,矛头蝮蛇毒引起了肾脏生理的强烈改变,包括与利尿、利钠和利钾相关的血管阻力下降。与全毒液相比,Bmtx-I在PP和RVR参数上表现出相反的作用。Bmtx-II对%TK(+)有轻微影响。Bmtx-II不能像Bmtx-I那样诱导肾脏效应,这一明显现象应归因于Bmtx-II缺乏富含C末端赖氨酸的区域。