Govendir Merran, Canfield Paul J, Church David B
Faculty of Veterinary Science, The University of Sydney, Australia.
Exp Toxicol Pathol. 2003 Sep;55(2-3):129-35. doi: 10.1078/0940-2993-00306.
d,l-Ethionine produces pancreatic exocrine necrosis and islet proliferation in hamsters and dogs. As a first step in examining whether induction of islet proliferation has therapeutic applications in animals with exhausted or destroyed insulin-producing beta-cells, we studied pancreatic cellular proliferation after intravenous administration of d,l-ethionine in normal dogs. Double immunohistochemical labelling of pancreatic tissue was used to identify proliferating cells in three groups of six clinically normal crossbred dogs administered d,l-ethionine (100 mg/kg) intravenously three times a week for two weeks. Six additional dogs served as untreated controls. Group I was euthanased and necropsied on day 15 (72 hours after the final dose of ethionine). Groups II and III were euthanased on days 29 and 43 respectively. Utilising markers for proliferating nuclei, insulin and cytokeratin, proliferating cells were classified as acinar, endocrine (both intra or extra-islet), duct or 'other' (i.e. infiltrative or interstitial) and counted under the light microscope (40x magnification). Compared to controls, an increase in the number of proliferating cells was found in all categories except ducts. Acinar cells demonstrated statistically significant (p < 0.05) proliferation, greatest two weeks after ethionine cessation continuing over four weeks. The interstitial, infiltrative or 'other' group also showed proliferation, however this was a more immediate response, which substantially decreased two weeks after ethionine administration. Endocrine cells showed only minor and non-significant proliferative activity and were probably not responsible for a significant increase in apparent beta-cell mass. The number of proliferating duct cells was inconsequential and there appeared to be no specific relationship between any cell populations and duct cells.
消旋乙硫氨酸可导致仓鼠和犬的胰腺外分泌坏死及胰岛增殖。作为研究胰岛增殖诱导在胰岛素分泌β细胞耗竭或破坏的动物中是否具有治疗应用的第一步，我们研究了正常犬静脉注射消旋乙硫氨酸后胰腺细胞的增殖情况。对三组各6只临床正常的杂种犬静脉注射消旋乙硫氨酸（100mg/kg），每周3次，共2周，采用胰腺组织双重免疫组化标记来鉴定增殖细胞。另外6只犬作为未处理的对照。第I组在第15天（最后一剂乙硫氨酸后72小时）实施安乐死并进行尸检。第II组和第III组分别在第29天和第43天实施安乐死。利用增殖细胞核、胰岛素和细胞角蛋白标记物，将增殖细胞分类为腺泡、内分泌（胰岛内或胰岛外）、导管或“其他”（即浸润性或间质细胞），并在光学显微镜（40倍放大）下计数。与对照组相比，除导管外，所有类别中的增殖细胞数量均增加。腺泡细胞表现出统计学显著（p<0.05）的增殖，在乙硫氨酸停用后2周时增殖最明显，并持续4周以上。间质、浸润性或“其他”组也显示出增殖，但这是一种更即时的反应，在乙硫氨酸给药后2周时大幅下降。内分泌细胞仅表现出轻微且无统计学意义的增殖活性，可能并非导致明显β细胞量显著增加的原因。增殖导管细胞的数量无关紧要，且任何细胞群与导管细胞之间似乎均无特定关系。
