Toll样受体3及肿瘤坏死因子α与特发性胎儿生长受限发病的关系

Correlation of toll-like receptor 3 and tumor necrosis factor-α with idiopathic fetal growth restriction

目的探讨妊娠特发性胎儿生长受限（IFGR）产妇胎盘组织中Toll样受体3（TLR-3）、产妇外周血及新生儿脐血中肿瘤坏死因子α（TNF—α）的表达变化及其与匀称型及非匀称型IFGR发病的关系。方法选择2008年4月—2009年4月在郑州大学第三附属医院妇产科分娩的42例单胎初产妇及其IFGR患儿为研究对象，均以足月剖宫产术分娩。按重量指数（PI）分型法分为匀称型20例（匀称型组），非匀称型22例（非匀称型组）。另随机选取足月正常产妇42例及其新生儿为对照组，均因骨盆狭窄或社会因素行剖宫产术分娩。采用免疫组化即用型非生物素二步法检测各组产妇胎盘组织中TLR-3蛋白表达；采用酶联免疫吸附试验检测各组产妇外周血及新生儿脐血中的TNF-α水平。结果（1）3组产妇胎盘组织中均有TLR-3蛋白不同程度的阳性表达，对照组及匀称型组TLR-3蛋白主要定位于胎盘合体滋养细胞、绒毛间质Hofbouer细胞胞质和（或）胞膜中；非匀称型组TLR-3蛋白主要定位于绒毛间质Hofbouer细胞胞质中，合体滋养细胞中有少量表达。（2）匀称型组及非匀称型组胎盘合体滋养细胞中的TLR-3蛋白表达水平分别为111±14及118±11，均明显低于对照组的156±9，分别比较，差异均有统计学意义（P〈0．01）。匀称型组胎盘绒毛间质Hofbouer细胞中的TLR-3阳性细胞数为（8．9±2．8）个，明显低于对照组的（17．5±2．8）个，两组比较，差异有统计学意义（P〈0．01）；非匀称型组胎盘绒毛间质Hofbouer细胞中的TLR-3阳性细胞数为（23．8±3．7）个，明显高于对照组，两组比较，差异有统计学意义（P〈0．01）。（3）匀称型组及非匀称型组产妇外周血中TNF-α水平分别为（90±10）及（86±11）μg／L，均明显高于对照组的（73±9）μg／，L，分别比较，差异均有统计学意义（P〈0．01）；匀称型组及非匀称型组新生儿脐血中TNF—α水平分别为（92±2）及（96±8）μg／L，均明显高于对照组的（79±9）μL，分别比较，差异均有统计学意义（P〈0．01）。（4）匀称型组产妇外周血中TNF-α水平与新生儿脐皿中TNF-α水平无相关性（r=-0．366，P〉0．05）；非匀称型组产妇外周血中TNF-α水平与新生儿脐血中TNF—α水平也无相关性（r=-0．273，P〉0．05）。（5）匀称型组及非匀称型组产妇外周血中TNF-α水平与Hofbouer细胞中TLR-3蛋白表达水平无相关性（P〉0．05）；新生儿脐血中TNF-α水平与Hofbouer细胞中TLR-3蛋白表达水平呈正相关关系（P〈0．05）。结论（1）胎盘组织中TLR-3表达紊乱及其脐血中TNF—α水平升高与IFGR发病相关；（2）匀称型IFGR的发生可能与Hofbouer细胞中TLR-3蛋白表达水平降低有关，非匀称型IFGR的发生可能与Hofbouer细胞中TLR-3蛋白表达水平升高有关。

Objective To investigate the expression and the significance of toll-like receptor 3 （TLR-3） in placenta, tumor necrosis factor-α（TNF-α） in maternal and cord blood of idiopathic fetal growth restriction （IFGR）, and their correlation with the pathogenesis of symmetric and asymmetric IFGR. Methods From April 2008 to April 2009, 42 primiparae of singleton pregnancy and their IFGR babies, who delivered at term through cesarean section, in the Third Affiliated Hospital of Zhengzhou University were enrolled. All subjectects were divided into symmetric IFGR group （n = 20） and asymmetric IFGR group （n = 22）. Another 42 non-IFGR pairs were randomly selected as the control group. The polink-2 plus polymerized horseradish peroxidase （HRP） immuuohistochemical method and the enzyme linked immunosorbent assay （ELISA） were applied to detect TLR-3 and TNF-α levels. Results （ 1 ） The expression of TLR-3 protein were observed in all maternal placenta of the three groups. TLR-3 essentially expressed in syncytiotrophoblasts and hofbouer cells in the symmetric IFGR and control group, but expressed mostly in hofbouer cells and less in syncytiotrophoblasts in the asymmetric IFGR group. （2） The expression of TLR-3 in the syncytiotrophoblasts of the symmetric and asymmetric IFGR group was significantly lower than in the control group （ 111 ± 14 and 118 ± 11 vs. 156 ±9, P 〈0. 01 ）. The number of TLR-3 positive in Hofbourer cell in the symmetric IFGR group was lower than the control group （8. 9 ± 2. 8 vs 17.5 ± 2. 8, P 〈 0. 01 ）, but the number in the asymmetric IFGR group was higher （ 23.8 ± 3.7） compared with the control group （ P 〈 0. 01）. （5） The TNF-α levels in the maternal and cord blood of the symmetric and the asymmetric group were higher than that of the control group [maternal： （90 ± 10） μg/L and （86 ± 11） μg/l, vs. （73 ±9） μg/L; cord blood： （92±12） μg/L and （96±8） μg/L vs. （79±9） μg/L; P〈0.01]. （4） Neither symmetric nor the asymmetric IFGR group showed any correlations between the maternal and cord blood levels of TNF-α （ P 〉 0. 05 ）. （ 5 ） Significant correlation was found between the TNF-α level of the cord blood and TLR-3 expression in the placenta in both the symmetric and asymmetric IFGR group（ P 〈0.05 ） , but no relationship was found between the maternal blood TNF-α level and TLR-3 expression in the placenta （ P 〉 0. 05）. Conclusions The variantions of TLR-3 expression in placenta and the increased expression of TNF-α in cord blood are associated with the genesis IFGR. The reduced expression of TLR-3 may related to symmetric IFGR, while the increased TLR-3 level in hofbouer cells may lead to asymmetric IFGR.