孕期咖啡因暴露所致的子代老年大鼠骨关节炎易感现象及其宫内编程机制  

Prenatal Caffeine Ingestion-Induced Susceptibility to Osteoarthritis and the Underlying Mechanism in Intrauterine Growth Retardation Rats

作　　者：曾一繁 王林龙[1] 罗瀚文[1] 谭杨[1] 李宁[1] 李孝海[1] 汪晖[2] 陈廖斌[1] 

机构地区：[1]武汉大学中南医院骨科,湖北武汉430071 [2]武汉大学基础医学院药理学系,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2014年第6期830-834,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金重大国际合作项目(编号:81220108026)

摘　　要：目的:观察孕期咖啡因暴露(PCE)所致宫内发育迟缓(IUGR)子代大鼠老年骨关节炎(OA)易感性的影响及其可能发生机制。方法:建立孕期咖啡因暴露所致子代大鼠IUGR模型,出生断乳后给予高脂饮食,饲养至12月时给予6周跑步刺激,18个月时麻醉处死大鼠。通过大体标本墨汁负染与病理学Modified Mankin评分等评估OA严重程度,并利用免疫组化技术检测关节软骨IGF-1信号通路表达变化。结果:与对照组相比,PCE组大鼠出现典型OA症状,Mankin评分升高(P<0.05),软骨基质浅染,胶原减少,免疫组化结果表明,IGF-1和IRS-2表达下调(P<0.05),而IGF-1R和AKT1/2表达无明显改变。结论:PCE可增加子代老年大鼠OA的易感性,其发生机制可能与宫内关节软骨IGF-1/IRS-2信号通路的低表达编程有关。Objective：To investigate the effects and possible mechanism of prenatal caffeine exposure（PCE）induced susceptibility to osteoarthritis（OA）in the elder offspring rats with intrauterine growth retardation（IUGR）.Methods：Rat model of IUGR was established by fed caffeine（120mg/kg/d）from gestational day 11 until delivery,the offsprings were fed with high-fat diet from the ablactation to 5.5 months,and running stimulation was given since 12 months old for 6weeks.OA severity assessment of articular cartilage was evaluated by gross specimen india-ink stain and pathological Modified Mankin＇s score,and the gray analysis of immunohistochemical assays were performed to determine the expression levels of IGF-1/IRS-2signal pathway protein in articular cartilage.Results：Comparing to the control group,rats in the caffeine group showed typical osteoarthritis symptoms,increased Mankin＇s score,cartilage matrix light staining and decreased collagen expression.The gray analysis of immunohistochemical assays showed that theexpression of IGF-1and IRS-2decreased（P〈0.05）,but AKT1/2and IGF-1Rhad no significant change.Conclusion：PCE induces an increased susceptibility to OA in the elder offspring,and its mechanism may be associated with the low expression programming of IGF-1/IRS-2signaling pathway in utero.

关 键 词：咖啡因 宫内发育迟缓 骨关节炎 胰岛素样生长因子-1 

分 类 号：R684.3[医药卫生—骨科学]