Ponraj D, Gopalakrishnakone P
Department of Anatomy, Faculty of Medicine, National University of Singapore, Singapore.
Kidney Int. 1997 Jun;51(6):1956-69. doi: 10.1038/ki.1997.267.
The renal lesions at various time intervals after i.m. injection of Pseudechis australis myotoxin (PA myotoxin) causing myoglobinuria in mice was studied. Biochemical assay of serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) showed marked elevations [7166 +/- 2064 IU and 1626 +/- 211 Berger-Broida U/ml (B-B U/ml)] six hours after injection, indicative of rhabdomyolysis. Serum creatinine (1.6 +/- 0.39) and urea (147 +/- 40) showed significant rise by 48 hours indicative of acute renal failure (ARF). Immunodiffusion showed the presence of myoglobin in the urine (myoglobinuria) of experimental animals. Light microscopic (LM) and scanning electron microscopic (SEM) studies of the urinary sediments from experimental mice revealed granular casts of varying size and shape. LM of kidney showed casts from one hour and tubulopathy with degenerated tubular epithelial cell from 12 hours onwards. Focal glomerular changes, such as dilated Bowman's space with poorly stained substance and reduction in number of glomerular tufts were observed. Immunofluorescence microscopy for myoglobin showed fluorescence of the casts in the tubules. Transmission electron microscopy (TEM) showed electron dense casts occupying the entire lumen of the distal convoluted tubules (DCT). The proximal convoluted tubules (PCT) showed features of proximal tubular necrosis (PTN). There was reduction in the basal infolding with activation of lysosomal system in the PCT. The glomeruli showed changes in the visceral epithelium that included intracellular edema, vesiculation and occasional fusion of the podocytes. Numerous granular materials were observed in the Bowman's space as well as in the lumen of the capillaries from 1 to 24 hours. Electron dense deposits of the glomerular basement membrane (GBM) capillaries were observed from 1 to 24 hours. SEM study revealed loss of microvilli of the PCT and some tubular lumen were filled with cast like material. Some glomeruli displayed a relatively flattened podocytes with thickened major foot processes. Regeneration of the tubules were seen from three weeks onwards.
研究了肌肉注射澳大利亚拟眼镜蛇肌毒素（PA肌毒素）致小鼠肌红蛋白尿后不同时间间隔的肾脏病变。血清肌酸磷酸激酶（CK）和乳酸脱氢酶（LDH）的生化检测显示，注射后6小时显著升高[分别为7166±2064 IU和1626±211贝格尔 - 布罗伊达单位/毫升（B - B U/ml）]，提示横纹肌溶解。血清肌酐（1.6±0.39）和尿素（147±40）在48小时时显著升高，提示急性肾衰竭（ARF）。免疫扩散显示实验动物尿液中存在肌红蛋白（肌红蛋白尿）。对实验小鼠尿沉渣进行光镜（LM）和扫描电镜（SEM）研究，发现大小和形状各异的颗粒管型。肾脏光镜检查显示1小时出现管型，12小时起出现肾小管病变及肾小管上皮细胞变性。观察到局灶性肾小球改变，如鲍曼囊扩张伴染色不佳物质以及肾小球簇数量减少。肌红蛋白免疫荧光显微镜检查显示肾小管管型有荧光。透射电子显微镜（TEM）显示电子致密管型占据远曲小管（DCT）整个管腔。近曲小管（PCT）显示近端肾小管坏死（PTN）特征。PCT基底褶减少，溶酶体系统激活。肾小球显示脏层上皮改变，包括细胞内水肿、囊泡形成以及偶尔足细胞融合。1至24小时在鲍曼囊以及毛细血管管腔中观察到大量颗粒物质。1至24小时观察到肾小球基底膜（GBM）毛细血管有电子致密沉积物。扫描电镜研究显示PCT微绒毛缺失，一些肾小管管腔充满管型样物质。一些肾小球显示足细胞相对扁平，主要足突增厚。从三周起可见肾小管再生。
