Marcussen N, Ottosen P D, Christensen S, Olsen T S
University Institute of Pathology, Aarhus Kommunehospital, University of Aarhus, Denmark.
Lab Invest. 1989 Sep;61(3):295-302.
Chronic renal failure was induced by administering lithium orally to 14 newborn rats. Seven rats were treated for 8 weeks followed by 8 weeks without lithium (group Li/C) and seven for 16 weeks (group Li/Li). Plasma urea and renal concentrating ability were measured, and one kidney fixed by vascular perfusion. Mean glomerular volume as well as volumes of individual glomeruli were estimated. In addition, the structural integrity between the glomerulus and the proximal tubule was investigated on serial sections. No sclerotic glomeruli were present. Only 37.6 and 27.9% of the glomeruli in the Li/C and Li/Li groups, respectively, were connected to a normal proximal tubule, and most remaining glomeruli were atubular. The mean glomerular volume was unchanged in the Li/C group and reduced by 40% in the Li/Li group. The intraindividual variation in glomerular volume was about 10-fold larger in the lithium-treated groups than in controls. The glomeruli connected to normal proximal tubules had the largest volumes, and hypertrophied glomeruli were encountered more frequently in the Li/C group than in the Li/Li group. There was a significant positive correlation between the plasma urea and the fraction of glomeruli that were not connected to normal proximal tubules. We previously demonstrated in this lithium model that there is a significant correlation between the tubulointerstitial lesion and the impairment of renal function. However, with the demonstration of atubular glomeruli we have a new explanation for the reduction in renal function in this model.
通过给14只新生大鼠口服锂来诱导慢性肾衰竭。7只大鼠接受8周治疗，随后8周不给予锂（Li/C组），另外7只大鼠接受16周治疗（Li/Li组）。测量血浆尿素和肾脏浓缩能力，并通过血管灌注固定一侧肾脏。估计平均肾小球体积以及单个肾小球的体积。此外，在连续切片上研究肾小球与近端小管之间的结构完整性。未发现硬化性肾小球。在Li/C组和Li/Li组中，分别只有37.6%和27.9%的肾小球与正常近端小管相连，其余大多数肾小球无肾小管相连。Li/C组的平均肾小球体积未改变，而Li/Li组减少了40%。锂处理组中肾小球体积的个体内变异比对照组大10倍左右。与正常近端小管相连的肾小球体积最大，且Li/C组中肥大性肾小球比Li/Li组更常见。血浆尿素与未与正常近端小管相连的肾小球比例之间存在显著正相关。我们之前在这个锂模型中证明，肾小管间质病变与肾功能损害之间存在显著相关性。然而，随着无肾小管相连肾小球的发现，我们对该模型中肾功能降低有了新的解释。
