Yamamoto Mitsuyoshi, Otani Munenori, Otsuki Makoto
Dept. of Gastroenterology and Metabolism, School of Medicine, Univ. of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Am J Physiol Gastrointest Liver Physiol. 2006 Oct;291(4):G700-8. doi: 10.1152/ajpgi.00502.2005.
This study was designed to examine whether continuous pancreatic ductal hypertension (PDH) plays an important role in the onset and development of chronic pancreatitis (CP). Pancreatic, biliary, and duodenal cannulas were implanted in male Wistar rats. PDH was induced by vertically raising the free end of the pancreatic duct cannula to exert a hydrostatic pressure and maintained for 2 wk. PDH was gradually increased, but when the pancreatic juice (PJ) flow was interrupted, PDH was decreased to restore PJ flow. The induction of PDH resulted in a marked reduction of amylase activity in PJ and an increase in serum amylase activity. At 2 wk after persistent PDH, pancreatic exocrine function was markedly decreased in response to a bolus injection of secretin (100 pmol/kg) compared with the control group. Histological examination revealed interlobular as well as intralobular fibrosis in the form of nodular pancreatitis at 2 wk after the induction of PDH. Immunohistochemistry revealed the expression of fibronectin and collagen types I and III. Quantitative real-time RT-PCR showed an increase in transforming growth factor-beta(1) mRNA expression in the pancreas during PDH. The present results suggest that PDH plays an important role in the onset and development of CP. Furthermore, our animal model seems useful for investigating the mechanisms of CP in rats.
本研究旨在探讨持续性胰管高压（PDH）在慢性胰腺炎（CP）的发生和发展过程中是否起重要作用。将胰管、胆管和十二指肠插管植入雄性Wistar大鼠体内。通过垂直抬高胰管插管的自由端以施加静水压力来诱导PDH，并维持2周。PDH逐渐升高，但当胰液（PJ）流动中断时，PDH下降以恢复PJ流动。PDH的诱导导致PJ中淀粉酶活性显著降低，血清淀粉酶活性升高。与对照组相比，在持续性PDH 2周后，给予大剂量注射促胰液素（100 pmol/kg）后，胰腺外分泌功能显著降低。组织学检查显示，在诱导PDH 2周后，胰腺呈现小叶间和小叶内纤维化，表现为结节性胰腺炎。免疫组织化学显示纤连蛋白以及I型和III型胶原蛋白的表达。定量实时逆转录聚合酶链反应显示，在PDH期间胰腺中转化生长因子-β(1) mRNA表达增加。目前的结果表明，PDH在CP的发生和发展中起重要作用。此外，我们的动物模型似乎有助于研究大鼠CP的发病机制。
