Graduate School, Tianjin Medical University, Tianjin, China.
Laboratory of Acute Abdomen Disease Associated Organ Injury and Repair, Nankai Hospital Affiliated to Nankai University, Tianjin, China.
Eur Surg Res. 2020;61(4-5):130-135. doi: 10.1159/000508270. Epub 2020 Dec 1.
The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates digestion and appetite, stimulates pancreatic growth, and participates in pancreatic carcinogenesis. The molecular mechanisms of CCK-induced effects are not fully understood. When the mechanisms are studied in animals, the surgical model of pancreatobiliary diversion (PBD) is frequently used. After animals have had PBD, their CCK secretion is no longer inhibited by pancreas-derived proteases, so circulating CCK is increased. PBD is established in rats and hamsters, but not in mice. In this study, we modified PBD procedures and established the model in the mouse. In an experiment, we performed PBD and sham operation (SO) in two groups of mice (20 mice per group). Twenty days after operation, 75% of the PBD mice and all SO mice survived. When plasma CCK was determined by radioimmunoassay, the PBD group had higher levels than the SO group (p < 0.001). To assess pancreatic growth, we determined pancreatic weight and pancreatic contents of protein and DNA. We also stained pancreatic sections by immunohistochemistry to show the proliferating cells that either expressed the proliferating cell nuclear antigen or were labeled with 5-bromo-2'-deoxyuridine. As a result, the pancreases of the PBD mice were heavier (p < 0.001) and had more protein (p < 0.001), DNA (p < 0.01), and proliferating cells (p < 0.01) than those of the SO counterparts. Thus, pancreatic growth was increased as a result of PBD-induced hypercholecystokininemia. The plasma and pancreatic data demonstrated that the PBD model was a success. This model may be used in CCK-related research. For instance, pancreatic cancer is frequently studied in transgenic mice. PBD may be combined with the cancer model to study the role of CCK in the molecular biology of pancreatic cancer.
胆囊收缩素（CCK）是一种主要由十二指肠和空肠近端的 I 细胞分泌的肠激素。食物消化会刺激 CCK 分泌，而胰腺分泌的蛋白酶会抑制其分泌。CCK 调节消化和食欲，刺激胰腺生长，并参与胰腺癌的发生。CCK 诱导效应的分子机制尚未完全阐明。在研究这些机制时，动物经常使用胰胆管分流术（PBD）的手术模型。动物接受 PBD 后，其 CCK 分泌不再受胰腺来源的蛋白酶抑制，因此循环 CCK 增加。PBD 可在大鼠和仓鼠中建立，但不能在小鼠中建立。在这项研究中，我们修改了 PBD 程序，并在小鼠中建立了该模型。在一项实验中，我们在两组小鼠（每组 20 只）中进行了 PBD 和假手术（SO）。术后 20 天，75%的 PBD 小鼠和所有 SO 小鼠存活。通过放射免疫法测定血浆 CCK 水平时，PBD 组高于 SO 组（p < 0.001）。为了评估胰腺生长，我们测定了胰腺重量以及胰腺蛋白和 DNA 含量。我们还通过免疫组织化学染色显示表达增殖细胞核抗原或被 5-溴-2'-脱氧尿苷标记的增殖细胞来染色胰腺切片。结果，PBD 小鼠的胰腺更重（p < 0.001），且蛋白（p < 0.001）、DNA（p < 0.01）和增殖细胞（p < 0.01）含量均高于 SO 组。因此，PBD 诱导的高胆囊收缩素血症导致胰腺生长增加。血浆和胰腺数据表明 PBD 模型取得了成功。该模型可用于 CCK 相关研究。例如，胰腺癌经常在转基因小鼠中进行研究。PBD 可与癌症模型结合使用，以研究 CCK 在胰腺癌分子生物学中的作用。
