PATHOGENESIS OF PANCREATIC ACINAR CELL DAMAGE AND POSSIBILIT OF INHIBITION : STUDIES WITH EXPERIMENTAL PANCREATITIS IN RATS

急性胰腺炎的发病机制仍有许多疑问。胰蛋白酶仍被认为发挥着重要作用。脂肪酶通过对甘油三酯的作用，释放出破坏完整细胞的游离酸。另一种脂溶酶磷脂酶A2，通过对卵磷脂的作用，释放溶卵磷脂，也破坏完整的细胞。在本研究中，我们利用表征良好的大鼠胰腺腺泡细胞模型来研究抑制急性细胞损伤的可能性。[方法]:1)将牛磺胆酸钠注入离体大鼠胰腺胰管，连续灌注缓冲液+/-尿胰蛋白酶抑制剂（UTI）或白蛋白。通过门静脉流出液中淀粉酶和脂肪酶的测定来评估器官损伤。2)在主胰管内注入生理盐水或5%牛胆酸钠。同时，在全胰腺间质注射HEPES-Ringered缓冲液或白蛋白。手术后6小时处死大鼠，观察胰腺脂肪及实质坏死的扩散情况。【结果】：条件1)白蛋白非常有效，能显著降低门静脉流出物中酶的释放。UTI是无效的。然而，当我们使用奥林巴斯图像分析系统进行组织学检查时，高浓度UTI显著降低了牛磺酸胆碱诱导的胰腺实质坏死和间质水肿。条件2)对照组胰腺大部因牛磺胆酸作用而坏死，在胰腺间质内注射HEPES-Ringered缓冲液。然而，当注射白蛋白时，通过胰管注射牛磺胆酸的胰腺坏死几乎被抑制。这些结果在组织学研究中得到证实。[结论]白蛋白与脂肪酸和溶卵磷脂等洗涤剂结合的能力可能具有治疗意义。尿路感染可能抑制急性胰腺炎的坏死和间质水肿。少

The pathogenesis of the acute pancreatitis still raises many questions. Trypsin is still thought to play an important role. Lipase, via its action on triglycerides, liberates free acids, which destroy intact cells. Another lipolytic enzyme phospholipase A2, via its action on lecithin, liberates lysolecithin, which also destroy intact cells. In the present study, we used the well characterized model of rat pancreatic acini to study possibilities to inhibit the acute cellular damage.[Methods] : 1) Sodium-taurocholate was injected into the pancreatic duct of isolated rat pancreas and the organ continuously perfused with buffer +/- either urinary trypsin inhibitor (UTI) or albumin. Organ damage was evaluated by measurement of amylase and lipase in the portal effluence. 2) Either normal saline or 5% sodium-taurocholate was injected into the main pancreatic duct. At the same time, either HEPES-Ringered buffer or albumin, was injected into the interstitium of the whole pancreas. Six hours aft … More er the operation, rats were killed and spread of fat and parenchymal necrosis of the pancreas was grossly and histologically examined.[Results] : Condition 1) Albumin was very effective and significantly lowered the release of enzymes into the portal venous effluence. UTI was ineffective. However, when we histologically examined using Olympus Image Analysis System, a high concentration of UTI significantly lowered both taurocholate-induced parenchymal necrosis and interstitial edema in the pancreas. Condition 2) Most of the pancreas was necrotic by the action of taurocholate in the control group, in which HEPES-Ringered buffer was injected into the interstitium of the pancreas. However, when albumin was injected, the necrosis of the pancreas by taurocholate injection of the pancreatic duct, was almost inhibited. These results were confirmed in the histological study.[Conclusion] Albumin may have therapeutical implications due to its ability to bind detergents such as fatty acids and lysolecithin. UTI might inhibit necrosis and interstitial edema in acute pancreatitis. Less