高迁移率族蛋白1及其受体晚期糖基化终末产物的表达与子痫前期发病的关系

Correlation between the expression of high mobility group box 1 and receptor for advanced glycation end products and the onset of pre-eclampsia

目的探讨高迁移率族蛋白1（HMGB1）及其受体晚期糖基化终末产物（RAGE）表达与子痫前期发病的关系。方法2006年3月至2007年3月中国医科大学附属盛京医院住院分娩的15例早发型子痫前期孕妇（早发型子痫前期组）、22例重度子痫前期孕妇（晚发型子痫前期组）、12例正常足月孕妇（正常对照组）。采用链霉亲和素-生物素-过氧化物酶复合物法检测3组孕妇胎盘组织中HMGB1和RAGE的蛋白定位及表达情况。结果（1）HMGB1蛋白定位及分布：正常对照组孕妇胎盘组织中无或仅有极少量HMGB1弱阳性细胞，主要见于滋养细胞层、单核巨噬细胞、蜕膜细胞、血管平滑肌细胞、血管内皮细胞和绒毛间质细胞，HMGB1在胞质内呈弥漫性分布，并呈略高于背景的淡棕黄色；晚发型子痫前期组孕妇胎盘组织中HMGB1阳性细胞分布与正常对照组一致，但HMGB1阳性细胞数量明显增多，染色强度也明显增强；早发型子痫前期孕妇胎盘组织中HMGB1主要分布于细胞滋养细胞，细胞核内可见深棕色染色，核膜皱缩。（2）RAGE蛋白定位及分布：正常对照组孕妇胎盘组织中无或仅有极少量RAGE弱阳性细胞，RAGE主要见于合体滋养细胞、血管内皮细胞，细胞膜和（或）细胞质内呈略高于背景的淡棕黄色染色；晚发型子痫前期组孕妇RAGE阳性细胞分布与正常对照组一致，但RAGE阳性细胞数量明显增多，染色强度也明显增强；早发型子痫前期组孕妇RAGE主要见于滋养细胞层，细胞呈RAGE强阳性表达。（3）HMGB1蛋白阳性表达率：早发型子痫前期组为73％（11／15），晚发型子痫前期组为64％（14／22），两组比较，差异无统计学意义（P〉0．05）；但两组均明显高于正常对照组的17％（2／12），差异有统计学意义（P〈0．05）。（4）RAGE蛋白阳性表达率：早发型子痫前期组为80％（12／15），晚发型子痫前期组为82％（18／22），两组比较，差异无统计学意义（P〉0．05）；但两组均明显高于正常对照组的25％（3／12），差异有统计学意义（P〈0．05）。结论子痫前期孕妇胎盘组织中的HMGB1和RAGE蛋白表达水平升高，可能是子痫前期发病的重要机制之一；HMGB1和RAGE在早发型和晚发型子痫前期孕妇胎盘组织中的表达部位不同，可能与不同临床类型的子痫前期发生有关。

Objective To evaluate different expressions of high mobility group box 1 （ HMGBI ） and receptor for advanced glycation end products （ RAGE ） in placentas and their relationship with pre- eclampsia. Methods Fifteen early-onset preeclamptic women （ early-onset pre-eclampsia group） , 22 lateonset pre-eclamptic women （late-onset pre-eclampsia group） and 12 normotensive women（ control group） in the third trimester were recruited at the Shengjing Hospital of China Medical University from March 2006 to March 2007. The localization and levels of HMGB1 and RAGE in placentas of the three groups were detected by the strept avidin biotin-peroxidase method. Results （ 1 ） Immunoreactivities to HMGB1 ： positive immunostaining for HMGB1 was observed in trophoblast, macrophages, decidual cells, vascular muscle cells, endothelial cells and placental mesenehvmal cells in the placentas from the pre-eclamptie women, while a low level of immunoreactivities was observed in the placentas from healthy pregnancies; the staining was observed within both the nuclei and the cytoplasm, mainly in the cytoplasm. The cytotrophoblast, especially the nuclei was extensively positive for HMGB1 in early-onset pre-eclampsia. （2） Immunoreactivities to RAGE： positive immunostaining for HMGB1 was observed in syneytiotrophoblast, macrophages and endothelial cells in the placentas from the preeclamptic women, while a low level of immunoreaetivities was observed in the placentas from healthy pregnancies; the staining was in the cytoplasm and（or） cell membrane. The trophoblast was extensively positive for RAGE in early-onset pre-eclampsia. （3） Positive rate of HMGBI expression： the expression of HMGB1 in early-onset group（73%, 11/15 ）and late-onset group（ 64%, 14/22 ） was significantly higher than that in normal group（ 17%, 2/12;P 〈 O. 05 ）, hut no significant difference was found in early-onset group and late-onset group （ P 〉 0. 05 ）. （4） Positive rate of RAGE expression： the expression of RAGE in early-onset group （80%, 12/15 ）and late-onset group （ 82 % , 18/22 ） was significantly higher than that in normal group （ 25 % ,3/12 ; P 〈 0. 05 ）, but no significant difference was found in early-onset group and late-onset group （ P 〉 0. 05 ）. Conclusions The increased expression of HMGBI and R_AGE in the placenta may play an important role in the pathogenesis of pre-eclampsia. The different locations may be associated with the occurrence of different onset types of pre-eelampsia.