Pancreas recovery following cerulein-induced pancreatitis is impaired in plasminogen-deficient mice
Pancreas recovery following cerulein-induced pancreatitis is impaired in plasminogen-deficient mice
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DOI：
10.1053/j.gastro.2006.06.023
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发表时间：
2006-09-01
期刊：
影响因子：
29.4
通讯作者：
Pandol, Stephen J.
中科院分区：
文献类型：
--
作者：
Lugea, Aurelia;Nan, Li;Pandol, Stephen J.
背景和目标：纤溶酶原（plg）系统参与组织修复的几个器官，但其在胰腺修复的作用仍然很差的特点。为了更好地理解plg在胰腺损伤后恢复中的作用，我们在plg缺乏和plg充足的小鼠中检测了蛙皮素诱导的胰腺炎的过程。方法：采用雨蛙肽（50 μ g/kg，7次腹腔注射）诱导胰腺炎模型。在急性期（第一次注射雨蛙肽后7小时）或恢复期（第2、4和7天）处死小鼠。在胰腺切片中，我们检查了胰腺形态、胰蛋白酶活化、炎性细胞浸润、腺泡细胞死亡、细胞增殖、细胞外基质沉积、星状细胞（PSC）的活化以及plg和金属蛋白酶系统的组分。结果：在plg充足的小鼠中，胰腺plg水平和纤溶酶活性在急性期增加，并在恢复期间保持升高。在plg充足的小鼠中，胰腺炎在7天内消退。胰腺恢复包括实质结构的重组、坏死碎片的去除、细胞增殖、PSC的瞬时活化和细胞外基质蛋白的中度沉积。急性胰腺炎（7小时）在plg缺乏和plg充足的小鼠之间是无法区分的。相反，plg缺陷小鼠的胰腺恢复受损。猪缺乏导致软组织紊乱，广泛的腺泡细胞损失，坏死碎片清除不良，细胞增殖减少和纤维化。纤维化的特征在于胶原和纤连蛋白的沉积、PSC的持续活化和胰腺转化生长因子β 1的上调。结论：Plg/纤溶酶缺乏导致与慢性胰腺炎相似的特征，如实质萎缩和纤维化。
Background & AIMS: The plasminogen (plg) system participates in tissue repair in several organs, but its role in pancreas repair remains poorly characterized. To understand better the role of plg in pancreas recovery following injury, we examined the course of cerulein-induced pancreatitis in plg-deficient and -sufficient mice. Methods: Pancreatitis was induced by cerulein administration (50 mu g/kg, 7 intraperitoneal injections). Mice were killed either at the acute phase (7 hours after the first cerulein injection) or during recovery (at 2, 4, and 7 days). in pancreatic sections, we examined pancreatic morphology, trypsin activation, inflammatory cell infiltration, acinar cell death, cell proliferation, extracellular matrix deposition, activation of stellate cells (PSCs), and components of the plg and metalloproteinase systems. Results: In plg-sufficent mice, pancreatic plg levels and plasmin activity increased during the acute phase and remained elevated during recovery. Pancreatitis resolved in plg-sufficient mice within 7 days. Pancreas recovery involved reorganization of the parenchyma structure, removal of necrotic debris, cell proliferation, transient activation of PSCs, and moderate deposition of extracellular matrix proteins. Acute pancreatitis (7 hours) was indistinguishable between plg-deficient and -sufficient mice. In contrast, pancreas recovery was impaired in plg-deficient mice. Pig deficiency led to disorganized parenchyma, extensive acinar cell loss, poor removal of necrotic debris, reduced cell proliferation, and fibrosis. Fibrosis was characterized by deposition of collagens and fibronectin, persistent activation of PSCs, and up-regulation of pancreatic transforming growth factor beta 1. Conclusions: Plg/plasmin deficiency leads to features similar to those found in chronic pancreatitis such as parenchyma 1 atrophy and fibrosis.