巨噬细胞移动抑制因子与受体CD74在胎盘组织中的表达及其与子痫前期发病的关系

Expression of macrophage migration inhibitory factor and CD_（74） in preeclamptic placenta and its correlation with preeclampsia

目的 探讨巨噬细胞移动抑制因子（MIF）与受体CD74在胎盘组织中的表达及其与子痫前期发病的关系.方法 选取2008年3-11月在青岛大学医学院附属医院产科住院分娩的子痫前期孕产妇69例,其中轻度子痫前期孕产妇33例（轻度子痫前期组）,重度子痫前期孕产妇36例（重度子痫前期组）.另选取同期正常妊娠晚期孕产妇43例为对照组.采用免疫比浊法榆测3组孕产妇血中C反应蛋白水平;采用免疫组化链酶菌抗生物素蛋白-过氧化物酶连接（SP）法榆测3组孕产妇胎枯组织中的MIF和CD74的表达;采用逆转录（RT）PCR技术检测3组孕产妇胎盘组织中MIFmRNA和CD74mRNA的表达.并对轻度及重度子痫前期组孕产妇血中C反应蛋白水平与胎盘组织中MIF mRNA及CD74 mRNA表达的相关性进行分析.结果 （1）3组孕产妇胎盘组织中均有MIF和CD74的表达,并呈棕黄色染色,轻度及莆度子痫前期组孕产妇胎盘组织中MIF及CD74的表达明显增强.（2）轻度子痫前期组孕产妇胎盘组织中MIF mRNA及CD74mRNA表达水平分别为0.70±0.13及0.96±0.16;重度子痫前期组分别为0.88±0.12及1.08±0.15,两组比较,差异有统计学意义（P〈0.01）.对照组孕产妇胎盘组织中MIF mRNA及CD74mRNA表达水平分别为0.67±0.11及0.83±0.14,明显低于轻度及重度子痫前期组,分别比较,差异均有统计学意义（P〈0.01）.（3）轻度及重度子痫前期组孕产妇血中C反应蛋白水平分别为（15.3±7.0）及（21.6±9.1）mg/L,两组比较,差异有统计学意义（P〈0.01）;对照组为（4.8±1.8）mg/L,明显低于轻度及重度子痫前期组,分别比较,差异均有统计学意义（P〈0.01）.（4）轻度及重度子痫前期组孕产妇血中C反应蛋白水平与胎盘组织中MIF mRNA表达呈正相关关系（r=0.67,P〈0.01）;与胎盘组织中CD74mRNA表达呈正相关火系（r=0.83,P〈0.01）.胎盘组织中MIF mRNA表达与CD74mRNA表达呈正相关关系（r=0.93,P〈0.01）.结论 子痫前期患者胎盘组织中的MIF及其受体CD74的过度表达,可上调血中炎性标志物C反应蛋白的水平,引起血管内皮损伤,从而参与子痫前期的发病.

Objective To investigate the expression of macrophage migration inhibitory factor （MIF） and CD_（74）, the receptor of MIF, in preeclamptic placenta and its correlation with the pathogenesis of preeclampsia.Methods From March 2008 to November 2008,69 preeclamptic women who delivered in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College,were recruited,including 33 women with mild preeclampsia （MPE group） and 36 women with severe preeclampsia （SPE group）.Another 43 healthy pregnant women were taken as control group.Immunoturbidimetry was applied to measure the concentrations of C-reactive protein （CRP） in maternal blood.The expressions of MIF and CD_（74） in placenta were tested with immunohistochemistry and the expressions of MIF mRNA and CD_（74） mRNA were detected by semiquantitative RT-PCR.The relationship between maternal blood level of CRP and MIF mRNA and CD_（74） mRNA in placenta was analyzed in the MPE and SPE group.Results （1） MIF and CD_（74） were expressed in the placenta of all pregnant women in the 3 groups, as shown in brown-yellow color, and significantly higher expression was found in the MPE and SPE group.（2） The expression of MIF mRNA and CD_（74） mRNA in the MPE group （0.70±0.13 and 0.96±0.16）, SPE group （0.88 ± 0.12 and 1.08 ± 0.15） were significantly higher than in the control group （0.67 ± 0.11 and 0.83 ± 0.14） （P 〈 0.01）, and statistical significance was also found between the MPE and SPE group （P 〈0.01）.（3）The maternal blood concentrations of CRP in the MPE and SPE group were significantly higher than in the control group [（15.3±7.0） mg/L and （21.6±9.1）mg/L vs （4.8 ± 1.8） mg/L, P 〈0.01] , and significant difference was also found between the MPE and SPE group （P 〈0.01）.（4） In the two preeclamptic groups, the blood concentrations of CRP were positively correlated with the expression of both MIF mRNA（r =0.67 ,P 〈0.01）and CD_（74） mRNA（r =0.83 ,P 〈0.01） in placenta.Positive correlation was also found between the levels of MIF mRNA and CD_（74） mRNA in placenta （r =0.93 ,P 〈 0.01）.Conclusions Overexpression of MIF and CD_（74） in the placenta may up-regulate the CRP level in maternal blood, resulting in systemic inflammatory reaction and vascular endothelium damage which may be involved in the pathogenesis of preeclampsia.