Pathogenesis of a rat model of chronic pancreatic insufficiency induced by injection of zein-oleic acid-linoleic acid solution into the pancreatic duct

采用大鼠胰管逆行注射玉米醇溶蛋白-油酸-亚油酸(0.05ml/100gbw)粘性溶液的方法建立慢性胰腺炎模型。一系列的显微镜检查显示，注射的溶液至少停留在24小时以上，主要是在交叉管中，部分在叶内管中，而在胆胰管中的溶液立即被冲出进入十二指肠。腺泡细胞早期超微结构改变为酶原颗粒减少，内质网扩张。在注入玉米醇溶蛋白溶液的小导管附近的实质内，24小时内出现腺泡腔增宽和细胞空泡化。1周时细胞高度进一步降低，腺泡腔扩张，间质水肿并伴有细胞浸润。腺泡变性表现为…后进展为管状复合体。在6个月的时间里，更多的ND导致明显的萎缩和不规则的纤维化和脂肪替代。6个月时可见胰管主干及其分支不规则扩张，并伴有胰管周围纤维化，注射后6h最高值的血清淀粉酶在第2天恢复正常，并持续6个月。随着时间的推移，治疗组大鼠体重逐渐增加，但胰腺重量下降(1周后下降33%，6周后下降69%，6个月后下降88%)。胰腺蛋白质、淀粉酶、DNA和RNA含量明显降低，胰腺重量明显减少，羟脯氨酸含量明显增加。BT-PABA试验6周为54%，6个月为22%。虽然6个月后胰腺IRI含量减少了四分之三，但未发生明显的糖尿病。基于这些结果，我们认为小导管的梗阻性改变可能在慢性胰腺炎的发生发展中起重要作用。较少

An experimental model of chronic pancreatitis was induced by a retrograde injection of the viscous solution consisting of zein-oleic acid-linoleic acid (0.05ml/100g BW) into the rat pancreatic duct. Serial microscopic studies revealed that the injected solution remained at least over 24 hr mainly in interlover ducts and partially in intralobar ducts, whereas the solution in the common bile-pancreatic duct was immediately washed out into the duodenum. The early ultra-structural changes of acinar cells were observed as decrease in zymogen granules and dilatation of the endoplasmic reticulum. Widening of acinar lumen and cellular vacuolization occurred within 24 hr at the parenchyma neighboring the small ducts filled with the zein-solution. Further decrease in cell height and dilatation of acinar lumen were accumulated and interstitial edema accompained with cellular infiltration was pronounced at 1 week. Degeneration of acini showing as tubular complexes appearance progressed afterward a … More nd led to marked atrophy with irregular fibrosis and fat replacement over a period of 6 months. In addition, irregular dilatation of major pancreatic duct and its branches with periductal fibrosis was observed at 6 months.Serum amylase level which was maximally increased 6 h after the injection was normalized on the second day and this level persisted for 6 months. As time passed, the treated rats gained weight gradually but pancreatic weight was reduced (-33% after 1 week, -69% after 6 weeks, -88% after 6 months). Pancreatic contents of protein, amylase, DNA and RNA were distinguishedly decreased as well as pancreatic weight, while hydroxyproline content was apparently increased. BT-PABA test was indicated as 54% at 6 weeks and 22% at 6 months. Although three quarters of pancreatic IRI content was lost after 6 months, overt diabetes did not occurred.Based on these results, it was considered that obstructive changes in the small ducts might play an important role in genesis and development of chronic pancreatitis. Less