Kakugawa Y, Giaid A, Yanagisawa M, Baynash A G, Melnyk P, Rosenberg L, Duguid W P
Department of Pathology, Montreal General Hospital and McGill University, Quebec, Canada.
J Pathol. 1996 Jan;178(1):78-83. doi: 10.1002/(SICI)1096-9896(199601)178:1<78::AID-PATH423>3.0.CO;2-N.
Chronic pancreatitis is characterized by the presence of an inflammatory infiltrate, progressive destruction of acinar cells, and fibrosis. The finding that endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic properties, reduces pancreatic blood flow in normal rats suggested that the peptide may be associated with the reduced pancreatic flow seen in animal models of chronic pancreatitis and in the morphological abnormalities of the disease. The aim of this study was to investigate sites of endothelin-1 expression in the pancreas of normal subjects and patients with chronic pancreatitis. The techniques of immunohistochemistry, in situ hybridization, and Northern blotting were used. Endothelin-1-like immunoreactivity was localized predominantly to islet cells both in normal subjects and in patients with chronic pancreatitis. Semi-quantitative analyses of immunostaining showed that endothelin-1-like immunoreactivity in islet cells of patients with chronic pancreatitis was greater than in normal subjects. Co-localization studies with glucagon, insulin, somatostatin, and pancreatic polypeptide showed that endothelin-1-like immunoreactivity co-exists with glucagon and insulin. There was no apparent co-existence of endothelin-1-like immunoreactivity with somatostatin or pancreatic polypeptide. Endothelin-1 mRNA was expressed in sites similar to those of the immunostaining, as well as in vascular endothelial cells. Northern blot analysis showed an increase in the expression of endothelin-1 mRNA in the patient population. There was a significant correlation between intensity of endothelin-1 immunostaining and severity of fibrosis in the patients with chronic pancreatitis. These findings suggest that an elevation in local expression of endothelin-1 may be associated with the morphological and haemodynamic changes of chronic pancreatitis.
慢性胰腺炎的特征是存在炎症浸润、腺泡细胞进行性破坏和纤维化。内皮素-1是一种具有血管收缩和促有丝分裂特性的内皮源性肽，它可减少正常大鼠的胰腺血流，这一发现提示该肽可能与慢性胰腺炎动物模型中所见的胰腺血流减少以及该疾病的形态学异常有关。本研究的目的是调查正常受试者和慢性胰腺炎患者胰腺中内皮素-1的表达部位。采用了免疫组织化学、原位杂交和Northern印迹技术。在正常受试者和慢性胰腺炎患者中，内皮素-1样免疫反应主要定位于胰岛细胞。免疫染色的半定量分析显示，慢性胰腺炎患者胰岛细胞中的内皮素-1样免疫反应强于正常受试者。与胰高血糖素、胰岛素、生长抑素和胰多肽的共定位研究表明，内皮素-1样免疫反应与胰高血糖素和胰岛素共存。内皮素-1样免疫反应与生长抑素或胰多肽没有明显的共存现象。内皮素-1 mRNA在与免疫染色相似的部位以及血管内皮细胞中表达。Northern印迹分析显示患者群体中内皮素-1 mRNA的表达增加。慢性胰腺炎患者中内皮素-1免疫染色强度与纤维化严重程度之间存在显著相关性。这些发现提示内皮素-1局部表达升高可能与慢性胰腺炎的形态学和血流动力学变化有关。
