Pathophysiological role of CCK in acute experimental pancreatitis

用抗增殖细胞核抗原（PCNA）或抗脱氧尿嘧啶（BrdU）抗体免疫金银染色法观察14天内胰腺腺泡细胞再生情况。PCNA标记指数（L.I.），血浆CCK活性在急性胰腺炎发病后第3天迅速升高，并在第11天持续高水平。急性胰腺炎再生期血浆CCK水平升高与Br dU L.I.显著相关。此外，长期服用CCK受体拮抗剂CR1505不仅明显抑制正常胰腺生长，而且抑制急性胰腺炎后腺泡再生。基于这些数据，可以得出结论，内源性CCK在腺泡细胞增殖中起重要作用，即使在急性胰腺炎。我们还用亚细胞分离的方法研究了CCK在急性胰腺炎细胞内发病机制中的作用。在雨蛙肽和精氨酸诱导的胰腺炎中，我们发现组织蛋白酶B重新分配到酶原组分中。胰蛋白酶原随后激活为胰蛋白酶被确认在胰腺炎，但不是在雨蛙素胰腺炎。CR 1505引起两种模型中组织蛋白酶B的再分布的轻微改善。CR1505对急性胰腺炎的保护作用在青色胰腺炎中获得，而在青色胰腺炎中没有。CCK在急性胰腺炎病理生理过程中的作用已被阐明，但对急性胰腺炎时腺泡细胞内事件的研究尚需进一步深入。

During 14 days in rats with arginine-induced acute pancreatitis, acinar cell regener ation was estimated by using immunogold-silver staining with anti-PCNA or anti-Br dU antibody. PCNA labeling index (L.I.), that was expressed as percentage of PCNA positive cells in 1000 acinar cells, indicated two major peaks on day 0.5 and 7 as well as Br dU L.I.Plasma CCK bioactivities which increased rapidly following the onset of acute pancreatitis reached the peak on day 3, and then continued high levels during 11 days. Increased levels of plasma CCK significantly correlated with Br dU L.I.during regenerative phase of acute pancreatitis. Furthermore, long-term administration of CR1505, a CCK receptor antagonist, apparently suppressed not only normal pancreatic growth but also acinar regeneration following acute pancreatitis. Based in these data, it is concluded that endogenous CCK plays an important role in acinar cell proliferation even in acute pancreatitis. We investigated also an role of CCK in intracellular pathogenesis of acute pancreatitis by using the method of the subcellular fractionation. In both caerulein- and arginine-induced pancreatitis, we found the redistribution of cathepsin B into zymogen fraction. Subsequent activation of trypsinogen to trypsin was recognized in arginine-pancreatitis but not in caerulein-pancreatitis. CR1505 caused minor improvement of the redistribution of cathepsin B in both model. Protective effect of CR1505 on acute pancreatitis was obtained in caerulein-pancreatitis and not in arginine-pancreatitis. The role of CCK on the pathophysiology of acute pancreatitis was clarified in the present study but we should study further the intracellular events in acinar cells in acutepancreatitis.