Perrien Daniel S, Wahl Elizabeth C, Hogue William R, Feige Ulrich, Aronson James, Ronis Martin J J, Badger Thomas M, Lumpkin Charles K
Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 722021, USA.
Toxicol Sci. 2004 Dec;82(2):656-60. doi: 10.1093/toxsci/kfi002. Epub 2004 Oct 6.
We tested the hypothesis that combined administration of IL-1 and TNF antagonists would protect fracture healing from inhibition by chronic ethanol exposure. Adult male rats were fed a liquid diet +/- ethanol (CON and ETOH) by intragastric infusion for three weeks prior to and three weeks after creation of an externally fixated tibial fracture. Beginning the day of fracture, one-half of each dietary group received 2.0 mg/kg/day IL-1ra and 2.0 mg/kg/2-days sTNFR1 (CON + ANTAG and ETOH + ANTAG), while all other animals received vehicle alone (CON + VEH and ETOH + VEH). Scoring of ex vivo radiographs and analysis by pQCT revealed a significantly lower incidence of bridging and reduced total mineral content in the ETOH + VEH group compared to all other groups. These results support, for the first time, the hypothesis that IL-1 and TNF antagonists are capable of protecting fracture healing from the inhibition associated with chronic ethanol consumption.
联合给予白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）拮抗剂可保护骨折愈合免受慢性乙醇暴露的抑制。成年雄性大鼠在进行外固定胫骨骨折手术前3周及术后3周，通过胃内灌注给予含或不含乙醇的液体饮食（分别为对照组和乙醇组）。自骨折当天起，每个饮食组的一半大鼠接受2.0mg/kg/天的IL-1受体拮抗剂（IL-1ra）和2.0mg/kg/每2天的可溶性TNF受体1（sTNFR1）（对照组+拮抗剂组和乙醇组+拮抗剂组），而所有其他动物仅接受溶剂（对照组+溶剂组和乙醇组+溶剂组）。离体X线片评分及外周定量计算机断层扫描（pQCT）分析显示，与所有其他组相比，乙醇组+溶剂组的骨痂桥接发生率显著降低，总矿物质含量减少。这些结果首次支持了以下假设：IL-1和TNF拮抗剂能够保护骨折愈合免受与慢性乙醇摄入相关的抑制作用。
