Kakugawa Y, Paraskevas S, Metrakos P, Giaid A, Qi S J, Duguid W P, Rosenberg L
Department of Surgery, Montreal General Hospital, Canada.
Pancreas. 1996 Jul;13(1):89-95. doi: 10.1097/00006676-199607000-00012.
Chronic pancreatitis (CP) is characterized by the presence of an inflammatory infiltrate with progressive destruction of acinar cells and fibrosis. The finding that endothelin-1 (ET-1), an endothelium-derived peptide having vasoconstrictive and mitogenic properties, reduces pancreatic blood flow (PBF) in normal rats suggested that the peptide may be associated with the reduced PBF seen in animal models of CP and with the morphological abnormalities of the disease. This study investigates changes in blood flow to the pancreas and other abdominal organs in a rat model of CP and compares ET-1 production in the pancreata of these rats and normal controls. CP was induced in male Wistar rats by the injection of oleic acid into the common bile/pancreatic duct. The radiolabeled microsphere technique was employed to measure blood flow to the pancreas, duodenum, liver, spleen, and kidneys. Immunohistochemistry was used to investigate the cellular production of ET-1. After 3 weeks, significant decreases were noted in body weight, pancreatic weight, and pancreatic DNA, amylase, and protein content in the animals with CP. PBF was reduced by 64% and duodenal blood flow by 80% relative to those in control animals. Hepatic and splenic blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flow was also seen in the experimental group after 3 weeks. Pancreata from animals with CP stained diffusely for ET-1 in the cytoplasm of vascular endothelial, acinar, and ductal cells. In the control pancreata, focal staining for ET-1 was observed only in acinar cells. This difference was significant in endothelial and ductal cells. There was weak staining of islet cells in both groups. The results suggest that elevation in local production of ET-1 may be associated with the morphological and hemodynamic changes of CP.
慢性胰腺炎（CP）的特征是存在炎性浸润，并伴有腺泡细胞的进行性破坏和纤维化。内皮素-1（ET-1）是一种具有血管收缩和促有丝分裂特性的内皮衍生肽，它可降低正常大鼠的胰腺血流量（PBF），这一发现提示该肽可能与CP动物模型中所见的PBF降低以及该疾病的形态学异常有关。本研究调查了CP大鼠模型中胰腺和其他腹部器官的血流变化，并比较了这些大鼠和正常对照胰腺中ET-1的产生情况。通过向雄性Wistar大鼠的胆总管/胰管注射油酸诱导CP。采用放射性微球技术测量胰腺、十二指肠、肝脏、脾脏和肾脏的血流量。免疫组织化学用于研究ET-1的细胞产生情况。3周后，CP动物的体重、胰腺重量、胰腺DNA、淀粉酶和蛋白质含量显著下降。与对照动物相比，PBF降低了64%，十二指肠血流量降低了80%。与对照相比，肝脏和脾脏血流量分别增加了91%和88%。实验组3周后肾血流量也下降了50%。CP动物的胰腺在血管内皮、腺泡和导管细胞的细胞质中弥漫性地染为ET-1阳性。在对照胰腺中，仅在腺泡细胞中观察到ET-1的局灶性染色。这种差异在内皮细胞和导管细胞中具有显著性。两组胰岛细胞均有弱阳性染色。结果表明，ET-1局部产生的升高可能与CP的形态学和血流动力学变化有关。
