Siegmund E, Jonas L, Borisch I, Fechner U, Käding U, Schröder H
Institute of Clinical Chemistry and Pathobiochemistry, Faculty of Medicine, University of Rostock, Germany.
Int J Pancreatol. 1998 Apr;23(2):125-36. doi: 10.1385/IJGC:23:2:125.
Acetylsalicylic acid (aspirin, ASA) in a therapeutic dose prevents lipid peroxidation and damage of cell organelles in pancreatic tissue of rats chronically fed with ethanol. In contrast, higher ASA dosages lead to enhanced biochemical and morphological signs of pancreatic damage different from findings in rats fed by ethanol alone.
Two groups of rats received 20% alcohol as drinking fluid plus a diet containing either 6 (S6) or 10 g/kg (S10) ASA. Two control groups received no ASA (CA) and neither ASA nor alcohol (CW), respectively. Feeding was performed by the interrupted feeding regimen with four 18-h periods of food and fluid withdrawal weekly. After 7 mo, pancreatic tissue was examined by light and electron microscopy. In pancreas homogenates, the contents of malondialdehyde (MDA), protein, trypsinogen, lipase, pancreatic secretory trypsin inhibitor, acid phosphatase (AcPh), cathepsin B, beta-glucuronidase, and desoxyribonucleic acid were determined.
In the pancreas of group CA, we found a 100% increase of MDA compared with group CW, increased fat deposition, as well as damaged mitochondria (Mito) and endoplasmic reticula (ER) in acinar cells, decreased protein content, decreased AcPh activity, and unchanged secretory parameters. The ASA-fed groups showed MDA contents indistinguishable from group CW. Protein and secretory parameters were decreased. Lysosomal enzymes were decreased in S6, but in S10, they were always higher than in group S6 and mostly as high as in group CW. Fat deposits were as frequent as in group CA. Mito and ER were mostly well preserved, but more autophagosomes and residual bodies occurred, particularly in group S10.
治疗剂量的乙酰水杨酸(阿司匹林,ASA)可预防长期摄入乙醇的大鼠胰腺组织中的脂质过氧化及细胞器损伤。相比之下,较高剂量的ASA会导致胰腺损伤的生化和形态学迹象增强,这与仅摄入乙醇的大鼠的研究结果不同。
两组大鼠饮用含20%乙醇的液体,并给予分别含6(S6)或10 g/kg(S10)ASA的饮食。两个对照组分别不给予ASA(CA)以及既不给予ASA也不给予乙醇(CW)。采用间断喂养方案,每周有4个18小时的禁食禁水期。7个月后,通过光镜和电镜检查胰腺组织。测定胰腺匀浆中丙二醛(MDA)、蛋白质、胰蛋白酶原、脂肪酶、胰腺分泌性胰蛋白酶抑制剂、酸性磷酸酶(AcPh)、组织蛋白酶B、β-葡萄糖醛酸酶和脱氧核糖核酸的含量。
与CW组相比,CA组胰腺中MDA含量增加了100%,脂肪沉积增加,腺泡细胞中的线粒体(Mito)和内质网(ER)受损,蛋白质含量降低,AcPh活性降低,分泌参数未改变。给予ASA的组MDA含量与CW组无差异。蛋白质和分泌参数降低。S6组溶酶体酶减少,但在S10组,它们总是高于S6组,且大多与CW组一样高。脂肪沉积与CA组一样频繁。Mito和ER大多保存良好,但出现了更多自噬体和残余体,尤其是在S10组。