Amelioration of Mesangial Volume and Surface Alterations Following Islet Transplantation in Diabetic Rats
Amelioration of Mesangial Volume and Surface Alterations Following Islet Transplantation in Diabetic Rats
复制标题
糖尿病大鼠胰岛移植后系膜体积和表面变化的改善
作者：
M. Steffes;David M. Brown;J. Basgen;S. Mauer
患有链脲佐菌素诱导的糖尿病7个月的高度近交Lewis大鼠接受了新生胰腺组织的门静脉内移植。在糖尿病第 7 个月和第 9 个月（胰岛移植时和胰岛移植后 2 个月），从对照大鼠 (C)、糖尿病非移植大鼠 (D) 和糖尿病移植大鼠 (D-T：血浆葡萄糖值正常) 获得肾活检，用于评估几个形态测量参数。 D-T 动物的肾小球体积在 9 个月时降至低于 C 大鼠的值，而 D 动物的肾小球体积在 7 个月和 9 个月时均超过 C 大鼠。总系膜及其细胞和基质成分的电子显微镜形态测定显示，与 C 组大鼠相比，D 组大鼠在 7 个月和 9 个月时系膜基质的体积增加了近两倍。虽然糖尿病中系膜细胞成分也增加，但 D 大鼠在 7 个月和 9 个月时系膜基质体积的变化提供了总系膜体积增加的主要部分。通过胰岛移植，系膜基质体积显着减少，细胞成分的减少小得多且不显着，从而使 D-T 动物中这些成分和总系膜体积的正常值。糖尿病中总系膜体积的扩大同时增加了与系膜交界的肾小球毛细血管表面的比例。同样，糖尿病患者中与系膜相邻的肾小球基底膜（GBM）-上皮界面的比例也升高。这两个观察结果表明，扩张的系膜将自身插入内皮细胞和 GBM 之间，从而增加了系膜的表面。通过胰岛移植，这些表面改变随着系膜体积的减少而恢复正常。这些电子显微镜形态测量的观察结果提供了实验性糖尿病系膜变化的详细记录。监测这些变化的灵敏度允许对糖尿病中系膜表面和体积的细微增加进行详细分析。
Highly inbred Lewis rats with streptozotocin-induced diabetes mellitus of 7 mo duration received intraportal transplants of neonatal pancreatic tissue. At 7 and 9 mo of diabetes (at the time of and at 2 mo after islet transplantation) renal biopsies for the evaluation of several morphometric parameters were obtained from control (C), diabetic-nontranspianted (D), and diabetic-transplanted (D-T: with normal plasma glucose values) rats. Glomerular volume in D-T animals at 9 mo fell to a value less than that in C rats while glomerular volume in D animals exceeded that in C rats at both 7 and 9 mo. Electron microscopic morphometry of the total mesangium and its cellular and matrix components documented a nearly twofold increase in the volume of the mesangial matrix in D as compared with C rats at both 7 and 9 mo. While the mesangial cellular component was also increased in diabetes, the changes in the volume of the mesangial matrix in D rats at both 7 and 9 mo provided the major proportion of the increased volume of the total mesangium. With islet transplantation, significant reduction in the volumes of the mesangial matrix and a much smaller and not significant decrease in the cellular component gave normal values for those components and for the volume of the total mesangium in D-T animals. The expanded volume of the total mesangium in diabetes concomitantly increased the proportion of the glomerular capillary surface interfaced with the mesangium. Similarly, the proportion of the glomerular basement membrane (GBM)-epithelium interface juxtaposed to the mesangium was elevated in diabetes. These two observations imply that the expanding mesangium interposed itself between the endothelial cells and the GBM, increasing the surface of the mesangium. With islet transplantation these surface alterations returned toward normal in conjunction with the reduction in volume of the mesangium. These observations with electron microscopic morphometry provide detailed documentation of the alterations in the mesangium of experimental diabetes mellitus. The sensitivity with which these changes can be monitored permit detailed analysis of subtle increases in both mesangial surface and volume in diabetes mellitus.