De Paepe M E, Keymeulen B, Pipeleers D, Klöppel G
Department of Experimental Pathology, Free University of Brussels, Belgium.
Hepatology. 1995 Apr;21(4):1144-53.
The liver offers an adequate site for the metabolic function of pancreatic islet implants. Little is known about the effects of the islet grafts on the host organ. This study examines liver tissue of normal or streptozotocin (STZ)-diabetic rats at different intervals following intraportal injection of syngeneic islets. Implantation of 800-islet-grafts, containing 0.9 million beta cells, normalized overt diabetes within 14 days. This period of metabolic normalization was characterized by a specific sequence of alterations in the implant area. During the first days after transplantation, islet cells migrated into the liver lobules, whereby tight hepatocyte-islet cell contacts were established. Hepatocytes surrounding grafts showed massive lipid accumulation and hypertrophy (cellular profile area 603 +/- 72 microns 2 in diabetic islet recipients vs. 382 +/- 42 microns 2 in diabetic controls; P < .005). The implant area also contained significantly more liver cells in proliferative activity than hepatic tissue in normal controls (bromodeoxyuridine labeling index of peri-islet hepatocytes 6.2%, 4.6%, and 0.9% on posttransplantation days 2, 4, and 14, respectively, compared with 0.02% in normal controls). The cellular hypertrophy and hyperplasia explain the sudden increase in liver weight of diabetic recipients (from 8.0 +/- 1.1 g to 13.8 +/- 2.2 g on posttransplantation day 2; P < .005). Both alterations can be attributed to the massive local discharge of insulin in an insulin-deficient organ containing an excess of extra-cellular nutrients. Progressive revascularization of the implant sites and overall metabolic normalization are thought to explain the return of a normal liver histology by the third week after transplantation. In conclusion, intraportal islet grafts exert profound effects on the liver of diabetic rat recipients. The morphological features of the implant sites may serve as markers for the function of the islet grafts as well as for the adaptive capacity of the recipient liver.
肝脏为胰岛移植提供了一个适合代谢功能发挥的场所。关于胰岛移植对宿主器官的影响，人们了解甚少。本研究在同基因胰岛经门静脉注射后的不同时间间隔，对正常或链脲佐菌素（STZ）诱导糖尿病大鼠的肝脏组织进行了检查。植入含有90万个β细胞的800个胰岛移植体后，明显的糖尿病在14天内恢复正常。这一代谢正常化时期的特点是移植区域出现特定的一系列变化。移植后的头几天，胰岛细胞迁移到肝小叶，从而建立了紧密的肝细胞 - 胰岛细胞接触。移植体周围的肝细胞出现大量脂质蓄积和肥大（糖尿病胰岛受体的细胞轮廓面积为603±72平方微米，而糖尿病对照组为382±42平方微米；P <.005）。与正常对照组的肝组织相比，移植区域增殖活性的肝细胞也明显更多（移植后第2天、第4天和第14天，胰岛周围肝细胞的溴脱氧尿苷标记指数分别为6.2%、4.6%和0.9%，而正常对照组为0.02%）。细胞肥大和增生解释了糖尿病受体肝脏重量的突然增加（移植后第2天从8.0±1.1克增加到13.8±2.2克；P <.005）。这两种变化都可归因于在一个细胞外营养物质过剩但胰岛素缺乏的器官中胰岛素的大量局部释放。移植部位的渐进性血管重建和整体代谢正常化被认为可以解释移植后第三周肝脏组织学恢复正常的原因。总之，门静脉内胰岛移植对糖尿病大鼠受体的肝脏有深远影响。移植部位的形态学特征可作为胰岛移植功能以及受体肝脏适应能力的标志物。
