蛋白酶抑制剂ONO-3403对胰泌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 secretin in rats

作　　者：陈少夫[1] 山本光勝 大槻眞 

机构地区：[1]中国医科大学第二临床学院消化内科,辽宁省沈阳市110004 [2]日本产业医科大学第三内科

出　　处：《世界华人消化杂志》2002年第7期792-795,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胰泌素刺激的胰腺外分泌的影响,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12h经胃管给与ONO-3403(20mg/kg)后收集基础的和静脉注射胰泌素后的胰液,并对胰腺组织匀浆处理。用Lowry法,产色素法分别测定胰液及胰腺组织中蛋白含量,淀粉酶含量。用DST800多项滴定系统测定胰液HCO_3^-含量。结果:给与ONO-3403的大鼠胰液容积,无论基础的及胰泌素刺激的,均较对照组明显增加,并在胰泌素每小时为125ng/kg时胰液容积达高峰(226±10ul per30min vs 44±5ulper 30min,P<0.01),提示ONO-3403能增加进食大鼠的胰液外分泌。给与ONO-3403的大鼠胰液蛋白含量与对照组相比,无论基础的和胰泌素刺激的均明显增加,并在胰泌素每小时为62.5ng/kg时胰液蛋白含量达高峰(985±215ug per 30min vs 254+47ug per30min,P<0.01),提示ONO-3403能增加进食大鼠的胰液外分泌中的蛋白含量。给与ONO-3403的大鼠胰液中MCO_3^-含量与对照组相比,无论基础的和胰泌素刺激的均明显增加,并在胰泌素每小时为250ng/kg时HCO_3^-含量达高峰(18±0.7umol per 30min vs 5.9±0.8umolper 30min,P<0.01),提示ONO-3403能增加进食大鼠的胰液中HCO_3^-含量。给与ONO-3403的大鼠胰腺重量和胰腺蛋白含量与对照组相比,差异不显著(P>0.05)。而胰腺淀粉酶含量与对照组相比明显降低(3114±372U×10~3 vs 5746±261U×10~3,P<0.05)。结论:ONO-3403能增加进食大鼠的胰腺外分泌及对胰泌素刺激的敏感性,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 secretin 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 12h before experiment. The pancreatic juice was collected before and after stimulation of stepwise increasing doses of secretin. The output of protein, amylase and bicarbonate in pancreatic juice or pancreatic tissue were determined by Lowry method, chromogenic method with blue-dyed starch polymer, and the DST 800 multititration system, respectively. RESULTS: Oral administration of ONO-3403 caused a significant increase in pancreatic juice flow (peak level 226±10 ul per 30min vs 44±5ul per 30 min, P<0.01), protein (peak level 985±215ug per 30min vs 254±47ug per 30min, P<0.01) and bicarbonate output (peak level 18±0.7umol per 30min vs 5.9±0.8umol per 30min,P<0.01) before and after secretin stimulation at 12h with pretreatment of ONO-3403. The pancreatic weight, pancreatic contents of protein in ONO-3403 pretreated rats were similar to those in control rats, and pancreatic content of amylasein in ONO-3403 pretreated rats was significantly lower than that in control rats (3114±372 U 10~3/Pancreas vs 5746±261U 10~3,p<0.05). CONCLUSIONS: ONO-3403 can increase pancreatic exocrine secretion and sensitivity to secretin stimulation. The mechanism of ONO3403 induced pancreatic exocrine hypersecretion may be feedback regulation of the pancreas by increasing CCK secretion.

关 键 词：蛋白酶抑制剂 ONO-3403 胰泌素刺激 大鼠 胰腺外分泌 

分 类 号：R576[医药卫生—消化系统]