Kimura W, Meyer F, Hess D, Kirchner T, Fischbach W, Mössner J
Department of Pathology, University of Würzburg, Germany.
Gastroenterology. 1992 Dec;103(6):1916-24. doi: 10.1016/0016-5085(92)91452-a.
Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate), and albumin under different conditions in rats were investigated. (a) Isolated pancreatic acini were incubated with pancreatic homogenates and triglycerides or lecithin with or without albumin and the degree of cellular destruction quantitated. (b) Taurocholate was injected into the pancreatic duct of isolated pancreas and the organ continuously perfused with either FUT, THL, or albumin. Organ damage was evaluated by measurement of pancreatic enzymes in the portal effluence. (c) Necrotizing pancreatitis was induced in vivo via retrograde taurocholate injection. FUT, THL, or albumin was applied either intravenously or injected into the pancreatic parenchyma. (a) Albumin prevented the cellular damage caused by both fatty acids and lysolecithin. (b) THL was ineffective, FUT lowered the release of pancreatic enzymes into the portal effluence, and albumin was most effective. (c) Albumin prevented the development of panlobular necrosis and lowered the degree of extrapancreatic fat necrosis. Albumin, via its ability to bind detergents, may have therapeutic implications.
脂解酶可能在急性胰腺炎的发病机制中起作用。因此,研究了脂肪酶抑制剂四氢脂抑素(THL)、蛋白酶抑制剂甲磺酸萘莫司他(FUT)和白蛋白在不同条件下对大鼠的影响。(a)将分离的胰腺腺泡与胰腺匀浆、甘油三酯或卵磷脂一起孵育,添加或不添加白蛋白,并对细胞破坏程度进行定量。(b)将牛磺胆酸盐注入分离胰腺的胰管,并使用FUT、THL或白蛋白对该器官进行持续灌注。通过测量门静脉流出液中的胰腺酶来评估器官损伤。(c)通过逆行注射牛磺胆酸盐在体内诱导坏死性胰腺炎。静脉注射FUT、THL或白蛋白,或将其注入胰腺实质。(a)白蛋白可防止脂肪酸和溶血卵磷脂引起的细胞损伤。(b)THL无效,FUT可降低胰腺酶向门静脉流出液中的释放,而白蛋白最为有效。(c)白蛋白可防止全小叶坏死的发展,并降低胰腺外脂肪坏死的程度。白蛋白通过其结合去污剂的能力可能具有治疗意义。