Menon Ramkumar, Fortunato Stephen J
Perinatal Research Center, Centennial Women's Hospital, 2300 Patterson St,Nashville, TN 37203, USA.
Am J Obstet Gynecol. 2009 Mar;200(3):334.e1-8. doi: 10.1016/j.ajog.2008.12.051.
The purpose of this study was to document distinct pathways that are initiated by lipopolysaccharide and cigarette smoke stimulation of normal term fetal membranes.
Fetal membranes from nonsmoking women at term, not in labor, from cesarean deliveries were placed in an organ explant system and stimulated with cigarette smoke extracts (CSEs), lipopolysaccharide, or lipopolysaccharide + CSE. Media were assayed for an interleukin (IL)-1beta, -1 receptor antagonist, -6, -8, -10, tumor necrosis factor alpha, soluble tumor necrosis factor receptors 1 and 2, and matrix metalloproteinases 1, 2, 3, 8, 9, and 12. Tissue homogenates were assayed for apoptotic markers (p53, caspase 3 activity, and cleaved poly [ADP-ribose] polymerase-1).
Lipopolysaccharide stimulation resulted in higher cytokine and matrix metalloproteinase concentrations, whereas it was lower after CSE and CSE + lipopolysaccharide stimulations, compared with control specimens. Apoptotic factors were several folds higher after CSE or CSE + lipopolysaccharide stimulation, compared with control specimens or lipopolysaccharide stimulations.
Cigarette smoke showed immunoinhibitory properties that potentially were mediated by apoptosis and lipopolysaccharide-induced proinflammatory response. This study demonstrated 2 independent pathophysiologic pathways that may alter pregnancy outcome.
本研究旨在记录正常足月胎膜受脂多糖和香烟烟雾刺激后启动的不同途径。
将剖宫产分娩的非吸烟足月未临产妇女的胎膜置于器官外植体系统中，用香烟烟雾提取物（CSE）、脂多糖或脂多糖+CSE进行刺激。检测培养基中的白细胞介素（IL）-1β、-1受体拮抗剂、-6、-8、-10、肿瘤坏死因子α、可溶性肿瘤坏死因子受体1和2以及基质金属蛋白酶1、2、3、8、9和12。检测组织匀浆中的凋亡标志物（p53、半胱天冬酶3活性和裂解的聚[ADP-核糖]聚合酶-1）。
与对照标本相比，脂多糖刺激导致细胞因子和基质金属蛋白酶浓度升高，而CSE和CSE+脂多糖刺激后浓度较低。与对照标本或脂多糖刺激相比，CSE或CSE+脂多糖刺激后凋亡因子高出几倍。
香烟烟雾显示出免疫抑制特性，可能由凋亡和脂多糖诱导的促炎反应介导。本研究证明了两条可能改变妊娠结局的独立病理生理途径。
