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存在许多问题。胰蛋白酶仍然被认为起着重要的作用。脂肪酶通过其对甘油三酯的作用，释放游离酸，其破坏完整的细胞。另一种脂解酶磷脂酶A2通过其对卵磷脂的作用释放溶血素，溶血素也破坏完整的细胞。在本研究中，我们使用了充分表征的大鼠胰腺腺泡模型来研究抑制急性细胞损伤的可能性。【方法】：1）将牛磺胆酸钠注射到离体大鼠胰腺的胰管中，并用缓冲液+/-尿胰蛋白酶抑制剂（UTI）或白蛋白持续灌注器官。通过测定门静脉流出物中的淀粉酶和脂肪酶来评估器官损害。2)将生理盐水或5%牛磺胆酸钠注入主胰管。同时，将HEPES-林格缓冲液或白蛋白注射到整个胰腺的回肠中。六小时后 ...更多信息 手术结束后处死大鼠，大体和组织学检查胰腺的脂肪扩散和实质坏死。[结果]：条件1）白蛋白能显著降低门静脉流出液中酶的释放。UTI无效。然而，当我们使用Olympus图像分析系统进行组织学检查时，高浓度的UTI显著降低了牛磺胆酸盐诱导的胰腺实质坏死和间质水肿。条件2）对照组在牛磺胆酸盐的作用下，胰腺大部分坏死，其中HEPES-林格缓冲液注入胰腺组织中。然而，当注射白蛋白时，胰管牛磺胆酸盐注射引起的胰腺坏死几乎得到抑制。这些结果在组织学研究中得到证实。[结论]白蛋白具有与脂肪酸、溶血素等去污剂结合的能力，可能具有治疗意义。UTI可抑制急性胰腺炎坏死和间质水肿。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