Fukumitsu K, Nakamura H, Otsuki M
Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyusyu.
Pancreas. 2001 Mar;22(2):179-85. doi: 10.1097/00006676-200103000-00011.
It is well-known that chronic oral administration of trypsin inhibitors induces pancreatic hypertrophy and hyperplasia via stimulation of endogenous cholecystokinin (CCK) release. Because the growth-promoting effect of CCK on the pancreas is specifically mediated by the CCK-A receptor, we examined the plasma CCK concentrations, the expression of CCK mRNA in the intestine and CCK-A receptor mRNA in the pancreas, and pancreatic growth in rats after chronic oral administration of synthetic protease inhibitor (PI). PI at a dose of 100 mg/kg body weight was administered via an orogastric tube once daily for 20 days. Plasma CCK concentrations at 24 hours after the first PI administration were significantly higher than those in randomly fed rats (6.57 +/- 0.67 pmol/L vs 4.31 +/- 0.51 pmol/L; p < 0.001), and further increased to 14.24 +/- 1.63 pmol/L after PI for 10 days and decreased to 10.05 +/- 0.72 pmol/L after 15 days of PI administration. Treatment with PI for 20 days significantly increased the pancreatic weight, and the total pancreatic protein and DNA content by 190%, 290%, and 170%, respectively, when compared to the control rats. Chronic oral administration of PI, however, reduced CCK-A receptor mRNA expression in the pancreas by 60%. These findings suggest that chronic oral administration of PI induces an elevation of endogenous CCK release and stimulates pancreatic growth, but down-regulates the biosynthesis of CCK-A receptor at the transcriptional level in the pancreas.
众所周知，长期口服胰蛋白酶抑制剂可通过刺激内源性胆囊收缩素（CCK）释放来诱导胰腺肥大和增生。由于CCK对胰腺的促生长作用是由CCK-A受体特异性介导的，我们研究了慢性口服合成蛋白酶抑制剂（PI）后大鼠的血浆CCK浓度、小肠中CCK mRNA的表达、胰腺中CCK-A受体mRNA的表达以及胰腺生长情况。以100mg/kg体重的剂量通过灌胃管每日给药一次，持续20天。首次给予PI后24小时的血浆CCK浓度显著高于随机喂养大鼠（6.57±0.67pmol/L对4.31±0.51pmol/L；p<0.001），给予PI 10天后进一步升高至14.24±1.63pmol/L，给予PI 15天后降至10.05±0.72pmol/L。与对照大鼠相比，给予PI 20天显著增加了胰腺重量、胰腺总蛋白和DNA含量，分别增加了190%、290%和170%。然而，长期口服PI可使胰腺中CCK-A受体mRNA表达降低60%。这些发现表明，长期口服PI可诱导内源性CCK释放增加并刺激胰腺生长，但在转录水平下调胰腺中CCK-A受体的生物合成。
