Cinel Ismail, Buyukafsar Kanso, Cinel Leyla, Polat Ayşe, Atici Sebnem, Tamer Lulufer, Oral Ugur
Department of Anesthesiology and Reanimation, Mersin University Faculty of Medicine, Adnan Menderes Bulvari, Marina Sitesi, C Blok, No: 4, Mersin, Turkey.
Pharmacol Res. 2002 Aug;46(2):119-27. doi: 10.1016/s1043-6618(02)00075-0.
In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO(3)(-)) levels were investigated. Thirty-two male Wistar rats, weighing 180-220g were randomly divided into four groups. The group I (control; n=8) received saline and group II (sepsis; n=8) received 10 mg kg(-1) LPS intraperitoneally. 3-AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and ileum samples were taken. Endotoxemic group exhibited significant apoptosis in intestinal epithelial cells and the immunohistochemical examination with M30 was demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum NO(3)(-) level was increased in endotoxemic group, whereas the elevation of NO(3)(-) level was prevented in LPS+3-AB group (P<0.05). The increased iNOS expression observed in the LPS group was also prevented by 3-AB. Compared with the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors should further be investigated as a new therapeutic alternatives in septic states.
在这种脂多糖（LPS）诱导的内毒素血症模型中，通过光学显微镜和M30细胞死亡染色评估了聚（ADP - 核糖）合成酶（PARS）抑制剂3 - 氨基苯甲酰胺（3 - AB）对回肠细胞凋亡的影响。此外，还研究了Bcl - 2、诱导型一氧化氮合酶（iNOS）表达与血清硝酸盐（NO₃⁻）水平之间的关系。将32只体重180 - 220g的雄性Wistar大鼠随机分为四组。第一组（对照组；n = 8）给予生理盐水，第二组（脓毒症组；n = 8）腹腔注射10 mg kg⁻¹ LPS。在给予LPS前20分钟给第四组（S + 3 - AB；n = 8）注射3 - AB，在给予生理盐水前20分钟给第三组（C + 3 - AB；n = 8）注射3 - AB。6小时后，采集血液和回肠样本。内毒素血症组肠道上皮细胞出现明显凋亡，M30免疫组化检查表明3 - AB可减少LPS诱导的肠道细胞凋亡。内毒素血症组血清NO₃⁻水平升高，而LPS + 3 - AB组可防止NO₃⁻水平升高（P < 0.05）。3 - AB还可阻止LPS组中观察到的iNOS表达增加。与内毒素血症组相比，LPS + 3 - AB组回肠上皮柱状细胞的Bcl - 2染色浓密，几乎与对照组相同。总之，3 - AB通过防止LPS诱导的Bcl - 2耗竭和阻断iNOS基因来减少LPS诱导的回肠细胞凋亡。作为脓毒症状态下新的治疗选择，应进一步研究PARS抑制剂对Bcl - 2表达的调节作用。
