Department of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Pancreas. 2012 Nov;41(8):1292-8. doi: 10.1097/MPA.0b013e31824c12f9.
Mutation in the Pkhd1 gene that encodes a ciliary protein, fibrocystin, causes multiple cysts in the kidneys and liver in the polycystic kidney (PCK) rat, a model for human autosomal recessive PCK disease. To clarify the role of primary cilia in the pancreatic duct, we examined the structure and function of the exocrine pancreas of PCK rats.
Pancreatic juice and bile were collected from anesthetized rats. Pancreatic ductal structure was analyzed by microdissection and immunohist0chemistry.
Histologically pancreatic acini were apparently normal, and no cysts were detected in the pancreas. Larger pancreatic ducts were irregularly dilated with enhanced expression of AQP1 in epithelial cells. The pancreatic duct of PCK rats exhibited significantly (P < 0.05) higher distensibility than that of wild-type (WT) rat at a physiological luminal pressure (3 cm H2O). Pancreatic fluid secretion stimulated with a physiological dose of secretin (0.03 nmol/kg per hour) in PCK rats was significantly smaller than that in WT, but the differences were not significant at higher doses. The amylase responses to carbamylcholine were not different between PCK and WT rats.
These findings suggest that fibrocystin/primary cilia-dependent mechanisms may play a role in the regulation of pancreatic ductal structure and fluid secretion.
PKHD1 基因编码纤毛蛋白——多囊蛋白 1，该基因突变会导致多囊肾病（PCK）大鼠的肾脏和肝脏出现多发性囊肿，该大鼠模型是人类常染色体隐性多囊肾病的模型。为了阐明初级纤毛在胰腺导管中的作用，我们研究了 PCK 大鼠的外分泌胰腺的结构和功能。
从麻醉大鼠中收集胰液和胆汁。通过显微解剖和免疫组织化学分析胰腺导管结构。
组织学上胰腺腺泡明显正常，胰腺内未发现囊肿。较大的胰腺导管不规则扩张，上皮细胞中 AQP1 的表达增强。在生理管腔压力（3cmH2O）下，PCK 大鼠的胰腺导管明显（P<0.05）具有更高的可扩张性。用生理剂量的缩胆囊素（0.03nmol/kg/小时）刺激时，PCK 大鼠的胰液分泌明显小于 WT 大鼠，但在更高剂量时差异不显著。PCK 和 WT 大鼠的胆堿能刺激的淀粉酶反应没有差异。
这些发现表明纤毛蛋白/初级纤毛依赖性机制可能在调节胰腺导管结构和液体分泌中发挥作用。
