Dombrowski F, Lehringer-Polzin M, Pfeifer U
Department of Pathology, University of Bonn, Germany.
Lab Invest. 1994 Nov;71(5):688-99.
Since insulin is known to have growth-promoting effects, it seemed of interest to study whether a local hyperinsulinemia after intraportal islet transplantation would induce a focal proliferation of the hepatocytes.
Four, 11, and 21 days after isologous intraportal transplantation of 450 to 1000 islets of Langerhans in streptocotocin-induced diabetic adult male Lewis-rats (n = 12) the animals were perfused with 3% glutaraldehyde, and the livers were cut into sections of 0.5-mm thickness. Stereomicroscopically the islets and the accompanying acini could be identified. These areas were prepared for histologic examination (1-micron-thick sections, staining by Richardson). The islets of Langerhans in the portal triads had induced remarkable changes (accumulation of fat and glycogen) of the hepatocytes in the respective acini. Therefore, it was possible to identify them for the examination of local cell proliferation. The mitotic index (number of mitotic figures per 1000 hepatocytic nuclei) and the apoptotic index (number of apoptotic bodies per 1000 hepatocytic nuclei) of these altered acini (A) were compared with the adjacent nonaltered acini (NA). In a further nine islet-transplanted diabetic animals 5-bromo-2'-desoxyuridine (BrdU) was applicated by osmotic minipumps for 6 days before death (6, 13, and 21, days after islet transplantation). The immunohistochemical labeling indices for BrdU (BrdU-labeled hepatocytic nuclei per 100 hepatocytic nuclei) of A and NA were compared.
The mitotic indices in A and NA were 1.2 and 0.06 at day 4, 2.5 and 0.09 at day 11, and 6.4 and 0.25 at day 21, respectively. The apoptotic indices in A and NA were 2.9 and 0.63 at day 4, 4.1 and 0.54 at day 11, and 8.0 and 0.5 at day 21, respectively. The BrdU labeling indices in A and NA were 28.0 and 1.3 at day 6, 37.0 and 1.9 at day 13, and 17.5 and 0.9 at day 21.
These data show that after intraportal islet transplantation the proliferative activity and at the same time the apoptotic elimination of hepatocytes are significantly increased focally in the long-term hyperinsulinemic liver acini.
由于已知胰岛素具有促进生长的作用，研究门静脉内胰岛移植后局部高胰岛素血症是否会诱导肝细胞局灶性增殖似乎很有意义。
在链脲佐菌素诱导的成年雄性糖尿病Lewis大鼠（n = 12）门静脉内同种异体移植450至1000个胰岛后的第4、11和21天，用3%戊二醛灌注动物，然后将肝脏切成0.5毫米厚的切片。通过体视显微镜可以识别胰岛及其伴随的腺泡。对这些区域进行组织学检查（1微米厚的切片，用Richardson染色）。门三联中的胰岛引起了相应腺泡中肝细胞的显著变化（脂肪和糖原积累）。因此，可以识别它们以检查局部细胞增殖。将这些改变的腺泡（A）的有丝分裂指数（每1000个肝细胞核中的有丝分裂象数）和凋亡指数（每1000个肝细胞核中的凋亡小体数）与相邻未改变的腺泡（NA）进行比较。在另外9只胰岛移植的糖尿病动物中，在死亡前6天（胰岛移植后6、13和21天）通过渗透微型泵给予5-溴-2'-脱氧尿苷（BrdU）。比较A和NA的BrdU免疫组化标记指数（每100个肝细胞核中BrdU标记的肝细胞核数）。
A和NA的有丝分裂指数在第4天分别为1.2和0.06，在第11天分别为2.5和0.09，在第21天分别为6.4和0.25。A和NA的凋亡指数在第4天分别为2.9和0.63，在第11天分别为4.1和0.54，在第21天分别为8.0和0.5。A和NA的BrdU标记指数在第6天分别为28.0和1.3，在第13天分别为37.0和1.9，在第21天分别为17.5和0.9。
这些数据表明，门静脉内胰岛移植后，长期高胰岛素血症的肝腺泡中肝细胞的增殖活性以及同时的凋亡消除均显著增加。
