Gao Lin, Liu Wen-Hui, Luan Nan-Nan, Feng Chong, Shang Tao
Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
Zhonghua Fu Chan Ke Za Zhi. 2008 Oct;43(10):746-50.
To evaluate different expressions of high mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) in placentas and their relationship with pre-eclampsia.
Fifteen early-onset pre-eclamptic women (early-onset pre-eclampsia group), 22 late-onset 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.
(1) Immunoreactivities to HMGB1: positive immunostaining for HMGB1 was observed in trophoblast, macrophages, decidual cells, vascular muscle cells, endothelial cells and placental mesenchymal cells in the placentas from the pre-eclamptic 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 syncytiotrophoblast, macrophages and endothelial cells in the placentas from the preeclamptic women, while a low level of immunoreactivities 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 HMGB1 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 < 0.05), but 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).
The increased expression of HMGB1 and RAGE 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-eclampsia.
评估晚期糖基化终末产物受体(RAGE)和高迁移率族蛋白B1(HMGB1)在胎盘中的不同表达及其与子痫前期的关系。
选取2006年3月至2007年3月在中国医科大学附属盛京医院就诊的孕晚期妇女,其中早发型子痫前期患者15例(早发型子痫前期组),晚发型子痫前期患者22例(晚发型子痫前期组),血压正常孕妇12例(对照组)。采用链霉亲和素生物素 - 过氧化物酶法检测三组胎盘组织中HMGB1和RAGE的定位及水平。
(1)HMGB1免疫反应性:子痫前期患者胎盘的滋养细胞、巨噬细胞、蜕膜细胞、血管平滑肌细胞、内皮细胞和胎盘间充质细胞中观察到HMGB1阳性免疫染色,而正常妊娠胎盘组织中免疫反应性较低;染色见于细胞核和细胞质内,主要在细胞质。早发型子痫前期患者的细胞滋养层,尤其是细胞核,HMGB1广泛呈阳性。(2)RAGE免疫反应性:子痫前期患者胎盘的合体滋养层、巨噬细胞和内皮细胞中观察到RAGE阳性免疫染色,而正常妊娠胎盘组织中免疫反应性较低;染色见于细胞质和(或)细胞膜。早发型子痫前期患者的滋养层RAGE广泛呈阳性。(3)HMGB1表达阳性率:早发型组(73%,11/15)和晚发型组(64%,14/22)HMGB1的表达显著高于正常组(17%,2/12;P<0.05),但早发型组与晚发型组之间差异无统计学意义(P>0.05)。(4)RAGE表达阳性率:早发型组(80%,12/15)和晚发型组(82%,18/22)RAGE的表达显著高于正常组(25%,3/12;P<0.05),但早发型组与晚发型组之间差异无统计学意义(P>0.05)。
胎盘中HMGB1和RAGE表达增加可能在子痫前期发病机制中起重要作用。不同的定位可能与子痫前期不同发病类型的发生有关。