ONO-3403对胆囊收缩素刺激的大鼠胰腺外分泌的影响  

Effects of protease inhibitor ONO-3403 on pancreatic exocrine response to CCK in rats

作　　者：陈少夫[1] 刘维新[2] 山本光勝 大槻真 

机构地区：[1]中国医科大学附属二院消化内科,辽宁省沈阳市110004 [2]中国医科大学第一临床学院消化内科,辽宁省沈阳市110001 [3]日本産業医科大学第三内科

出　　处：《世界华人消化杂志》2003年第6期737-740,共4页World Chinese Journal of Digestology

摘　　要：目的:观察新型蛋白酶抑制剂ONO-3403对进食大鼠基础的及CCK-8刺激的胰腺外分泌功能的影响,探讨ONO-3403增加胰腺外分泌的机制。方法:对进食的Wistar大鼠,分别于实验前6h和12h经胃管给与ONO-3403(20ug/kg)后收集基础的和静脉注射CCK-8后的胰液,并对胰腺组织进行匀浆处理,用Lowry法、产色素法和Whitaker法,分别测定胰液及胰腺组织中的蛋白含量,淀粉酶和脂肪酶含量。结果:(1)基础的及CCK-8刺激的12h组的胰液容积(峰值215±9ulper 30min vs 93±6ulper 30min,P<0.01),蛋白含量(峰值16475±1801ugper 30min vs 5920±593ugper 30min,P<0.01),均较对照组明显增加,而6h组无显著变化,(2)基础胰液中淀粉酶含量(6h组470±32super 30min P<0.01,12h组394±47super 30min P<0.05,较对照组251±32super 30min明显增加),,HCO_3^-含量(6h组2.224±0.333umolper 30 min P<0.05,12h组3.148±0.374umolper 30 min P<0.01,较对照组1.428±0.282umolper 30 min明显增加),而脂肪酶无显著的变化,(3)6h组和12h组的胰腺质量及胰腺组织中蛋白质,淀粉酶含量均无显著变化(P>0.05)。结论:ONO-3403能增加进食大鼠的胰腺外分泌及对CCK-8刺激的敏感性,其机制可能是通过CCK调节的胰腺反馈而起作用的。AIM: To examine the pancreatic exocrine response to CCK-8 and to clarify the mechanism of the pancreatic exocrine hypersecretion after oral administration of synthetic protease inhibitor ONO-3403 in rats. METHODS: A single oral dose of synthetic protease inhibitor ONO-3403 was given to rats by orogastric tube 6h and 12h before experiments. The pancreatic juice was collected before test and after stimulation of stepwise increasing doses of CCK-8. The output of protein, amylase, lipase and bicarbonate in pancreatic juice or pancreatic tissue were determinated by Lowry method, Chromogenic method with blue-dyed starch polymer, Whitaker method and by the DST 800 multititration system, respectively. RESULTS: Oral administration of ONO-3403 had no influence on pancreatic juice flow and output of protein in basal and CCK-8 stimulation at 6h after ONO-3403 pretreated, but it caused a significant increase in pancreatic juice flow(peak level 215±9 ulper 30 min vs93±6 ulper 30 min, P<0.01) and protein output (peak level 16475±1801ug per 30 min vs 5 920±593 ug per 30 min, P<0.01) of the basal and CCK-8 stimulation at 12 h after ONO-3 403 pretreated. The basal pancreatic juice flow and output of amylase(470±32 su per 30 min at 6 h P<0.01, 394±47 su per 30 min at 12 h, P<0.05 vs 251±_32 su per 30 min), bicarbonate (2.224±0.333 umolper 30 min at 6 h, P<0.05; 3.148±0.374 umolper 30 min at 12 h, P<0.01 vs 1.428±0.282 umolper 30 min) were significant high after ONO-3403 pretreated than those of control group. There was no change in lipase output compared with control group. The pancreatic weight, pancreatic contents of protein and amylase in ONO-3 403 pretreated rats were similar to those in control rats. CONCLUSION: ONO-3 403 can increase pancreatic exocrine secretion and sensitivity to CCK-8 stimulation.The mechanism of ONO3 403 induced pancreatic exocrine hypersecretion may be a feedback regulation of the pancreas by increasing CCK secretion.

关 键 词：ONO-3403 胆囊收缩素 大鼠 胰腺外分泌 蛋白酶抑制剂 淀粉酶 脂肪酶 胰腺炎 

分 类 号：R575.6[医药卫生—消化系统]