Lorenzo C, del Olmo Martinez M L, Pastor L, Almaraz A, Belmonte A, Caro-Patón A
Department of Medicine, Faculty of Medicine, University of Valladolid, Spain.
Int J Pancreatol. 1999 Dec;26(3):181-8. doi: 10.1385/ijgc:26:3:181.
Given the appearance of pancreatitis attributed to tetracycline, as described in the literature, we have investigated its effect on the enzymatic content of pancreas and duodenal fluid and on pancreatic ultrastructure. We have evaluated possible differences between sexes and the relation of our findings with those described in the initial phases of acute pancreatitis, in the context of the acinar hypothesis.
With 128 Wistar rats (63 male and 65 female), 3 groups were established: control (group I) experimental animals treated with oxytetracycline intramuscularly, 15 and 30 mg/kg/d (groups II and III, respectively). Before sacrifice, half of the rats in each group were stimulated with cholecystokinin. Blood, pancreatic tissue (for enzyme dosage and morphological study), and duodenal fluid were extracted following anesthesia.
The stimulated males of group III presented lower amylase levels in pancreatic tissue and duodenal fluid (P < 0.003). Just the opposite occurred in female rats. A similar tendency was observed with other enzymes (lipase and trypsin). Zymogen granule counts, appearance of immature granules, and dilation of ergastoplasm were more frequent in the stimulated animals.
Oxytetracycline seems to induce morphofunctional changes in rat pancreas, which differ according to sex. In the female, enzyme accumulation that could predispose intracellular activation seems to exist, as well as the ultrastructural findings described in initial phases of acute experimental pancreatitis. This agrees with the greater frequency of pancreatitis in women undergoing tetracycline treatment described in the literature. In contrast, for males the findings were more compatible with decrease of protein synthesis. This would make them less susceptible to crinophagy phenomena and, thus, to acute pancreatitis in the context of the acinar or lysosome hypothesis.
鉴于文献中所描述的四环素所致胰腺炎的表现,我们研究了其对胰腺和十二指肠液酶含量以及胰腺超微结构的影响。我们评估了性别之间可能存在的差异,以及在腺泡假说背景下,我们的研究结果与急性胰腺炎初始阶段所描述情况的关系。
选用128只Wistar大鼠(63只雄性和65只雌性),分为3组:对照组(I组);肌肉注射土霉素的实验动物组,剂量分别为15mg/kg/d(II组)和30mg/kg/d(III组)。在处死前,每组一半的大鼠用胆囊收缩素刺激。麻醉后采集血液、胰腺组织(用于酶定量和形态学研究)以及十二指肠液。
III组受刺激的雄性大鼠胰腺组织和十二指肠液中的淀粉酶水平较低(P<0.003)。雌性大鼠则相反。其他酶(脂肪酶和胰蛋白酶)也观察到类似趋势。受刺激动物中酶原颗粒计数、未成熟颗粒的出现以及内质网扩张更为常见。
土霉素似乎会诱导大鼠胰腺发生形态功能变化,且这种变化因性别而异。在雌性大鼠中,似乎存在可能导致细胞内激活的酶积累,以及急性实验性胰腺炎初始阶段所描述的超微结构改变。这与文献中描述的接受四环素治疗的女性胰腺炎发生率较高相一致。相比之下,雄性大鼠的研究结果更符合蛋白质合成减少的情况。这将使它们较不易发生自噬现象,从而在腺泡或溶酶体假说背景下不易发生急性胰腺炎。