Dirlik Musa, Caglikulekci Mehmet, Cinel Ismail, Cinel Leyla, Tamer Lülüfer, Pata Cengiz, Kanik Arzu, Ocal Koray, Ogetman Zekai, Aydin Süha
Department of General Surgery, Faculty of Medicine, Mersin University Medical School, Zeytinlibahçe Caddesi, Eski Otogar Yani 33079, Mersin, Turkey.
Pharmacol Res. 2003 Aug;48(2):139-49. doi: 10.1016/s1043-6618(03)00100-2.
In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.
在我们的实验研究中，我们调查了3 - 氨基苯甲酰胺（3 - AB），一种聚（ADP - 核糖）合成酶（PARS）抑制剂，对阻塞性黄疸（OJ）大鼠脂多糖（LPS）诱导的炎症中回肠组织病理学及细胞凋亡的保护作用。我们将40只大鼠随机分为五组。第1组：假手术组；第2组：OJ组；第3组：OJ + LPS组；第4组：OJ + 3 - AB + LPS组；第5组：OJ + LPS + 3 - AB组。在第5天时，大鼠出现黄疸。在第3组中，于第5天腹腔注射10 mg/kg（-1）LPS，6小时后处死大鼠。在第4组中，于第5天腹腔注射10 mg/kg（-1）3 - AB，每日重复给药3天，在第8天腹腔注射10 mg/kg（-1）LPS。在第5组中，于第5天腹腔注射10 mg/kg（-1）LPS，6小时后腹腔注射10 mg/kg（-1）3 - AB，每日重复给药3天。在第8天，处死大鼠。采集血样检测血清丙二醛（MDA）水平。再次剖腹后取回肠样本进行组织病理学检查，以评估内毒素相关的肠道损伤及半胱天冬酶 - 3凋亡情况，并检测组织MDA和ATP酶活性。组织病理学检查显示，第3组和第5组的绒毛和隐窝上皮细胞有明显破坏且存在广泛凋亡。在第4组中，肠黏膜损伤和凋亡细胞的评分显著降低（P < 0.05）。另一方面，第5组的肠黏膜损伤和凋亡细胞评分未得到改善。给予3 - AB后（第4组），与第1组和第2组相比，血清和回肠MDA水平降低，回肠ATP酶增加。我们的研究表明，如果在LPS给药前给予3 - AB，可显著预防肠上皮细胞的黏膜损伤和凋亡性损失。然而，如果OJ中已存在内毒素血症，3 - AB不能显著预防肠上皮细胞的黏膜损伤和凋亡性损失。
