中文摘要：

目的观察孕期尼古丁暴露（prenatal nicotine exposure,PNE）所致宫内发育迟缓（intrauterine growth restriction,IUGR）子代大鼠老年期骨关节炎（osteoarthritis,OA）的易感性及机制。方法于大鼠孕11d起注射尼古丁[2mg/（kg·d）]至分娩。正常对照组及PNE子代IUGR大鼠断奶后至6月龄给予高脂饮食,16.5月龄时以长距离跑步6周诱发OA发生。取大鼠膝关节标本切片进行改良Mankin’s评分及免疫组化检测分析。结果与正常对照组相比,PNE组大鼠出现典型OA症状,如软骨基质浅染、软骨纤维化,Mankin评分显著升高（P〈0.05）,且关节软骨胰岛素样生长因子-1（IGF-1）蛋白水平表达下降（P〈0.05）。结论 PNE可致子代IUGR大鼠老年期OA易感,其机制可能与关节软骨IGF-1低表达编程有关。

英文摘要：

Objective To investigate the susceptibility of osteoarthritis（OA）and the underlying mechanism in the rat offspring with intrauterine growth retardation（IUGR）induced by prenatal nicotine exposure（PNE）.Methods Rats were subcutaneously injected with nicotine[2mg/（kg·d）]from gestational day 11 until delivery.The offspring rats were fed on high-fat diet from the ablactation to 6months old in both normal control and PNE groups.Forced running stimulation was administrated to offspring rats at 16.5months old for 6weeks to induce OA.The knee joints were removed for the Modified Mankin＇s scoring and immunohistochemistry analysis.Results Offspring rats in PNE group showed typical OA features,such as weak staining of the articular cartilage matrix,increased fibrosis of the articular cartilage,and increased Mankin＇s scores.The immunohistochemical assay showed significantly reduced expression of IGF-1in PNE group when compared with the normal control group（P〈0.05）.Conclusion PNE increases the susceptibility to senile OA in offspring rats,which may be associated with the low expression of IGF-1in the articular cartilage.