Tukaj C, Olewniak-Adamowska A, Pirski M I, Woźniak M
Department of Electron Microscopy, Medical University of Gdansk, Poland.
Folia Morphol (Warsz). 2012 Aug;71(3):136-41.
Pathophysiology of acute pancreatitis (AP) has not been clearly established; nevertheless, accumulating evidence implicates highly reactive oxygen species (ROS) as important mediators of exocrine tissue damage. In this study, we used a water-soluble radical initiator, 2,2 -azobis-(2-amidinopropane) dihydrochloride (AAPH), to investigate the consequences of oxidative stress insult to the rat pancreas. The detailed characterisation of acini ultrastructural changes in the early course (3, 6, 12, 24 h) of AAPH-induced pancreatitis (40 mg/1 kg body weight) was performed. Considerable damage to the mitochondria in acinar cells manifested by increased translucence of the matrix, partial destruction of cristae, and formation of myelin figures were noted. At the same time, focal dilation, degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules was observed. The most prominent ultrastructural feature was accumulation of highly polymorphic cytoplasmic vacuoles in acinar cells. Double membrane-bound autophagosomes, different in size and shape, with sequestered organelles, autophagolysosomes, and large, empty, single-membrane-bound vacuoles were observed within the cytoplasm. The results indicate that intensive and impaired autophagy mediates pathological accumulation of vacuoles in acinar cells. The rat model of acute pancreatitis induced by AAPH is useful to investigate the early events of oxidative stress insult to the pancreas.
急性胰腺炎(AP)的病理生理学尚未明确确立;然而,越来越多的证据表明高活性氧物种(ROS)是外分泌组织损伤的重要介质。在本研究中,我们使用水溶性自由基引发剂2,2 -偶氮双(2-脒基丙烷)二盐酸盐(AAPH)来研究氧化应激损伤对大鼠胰腺的影响。对AAPH诱导的胰腺炎(40mg/1kg体重)早期病程(3、6、12、24小时)腺泡超微结构变化进行了详细表征。观察到腺泡细胞中线粒体有相当程度的损伤,表现为基质透明度增加、嵴部分破坏以及髓鞘样结构形成。同时,观察到粗面内质网局部扩张、脱颗粒以及酶原颗粒数量减少。最显著的超微结构特征是腺泡细胞中高度多形性的细胞质空泡积聚。在细胞质内观察到大小和形状各异的双膜结合自噬体,其中含有被隔离的细胞器、自噬溶酶体以及大的、空的、单膜结合的空泡。结果表明,强烈且受损的自噬介导了腺泡细胞中液泡的病理性积聚。AAPH诱导的大鼠急性胰腺炎模型对于研究胰腺氧化应激损伤的早期事件是有用的。