早发重度PE及HEELP综合征患者胎盘组织、母血、脐血中HMGB1和RAGP的表达观察

Expression of HMGB1 and RAGE in placenta,maternal serum and cord serum in patients with early-onset severe PE and HELLP syndrome

目的观察早发重度子痫前期(PE)及HELLP综合征患者胎盘组织、母血、脐血中高迁移率族蛋白1(HMGB1)和晚期糖基化终末产物受体(RAGE)的表达变化,探讨其与早发重度PE及HELLP综合征发病的关系。方法 30例早发重度PE患者(早发重度PE组)、12例HELLP综合征患者(HELLP组)、30例正常孕妇(对照组),分别采用免疫组化法、Western blotting法对三组胎盘组织中的HMGB1蛋白和RAGE蛋白进行定位及定量检测,采用实时定量PCR法对三组胎盘组织中HMGB1 mRNA和RAGE mRNA进行检测,采用ELISA对三组母血、脐血中的HMGB1蛋白和RAGE蛋白进行检测。结果对照组胎盘组织中仅有极少量HMGB1阳性合体滋养细胞,早发重度PE组HMGB1阳性细胞主要为合体滋养细胞和血管内皮细胞且阳性细胞数量明显增多,HELLP组HMGB1阳性细胞主要为合体滋养细胞、单核巨噬细胞、血管内皮细胞;对照组胎盘组织可见少量RAGE阳性合体滋养细胞、血管内皮细胞,早发重度PE组RAGE阳性细胞分布与对照组一致,HELLP组RAGE阳性细胞主要为合体滋养细胞、单核巨噬细胞(阳性细胞数量和表达强度均明显高于早发重度PE组)。早发重度PE组和HELLP组胎盘组织中HMGB1、RAGE的蛋白及mRNA表达明显高于对照组(P均<0.05),且HELLP组高于早发重度PE组(P均<0.05)。早发重度PE组和HELLP组母血HMGB1、RAGE蛋白水平明显高于对照组(P均<0.05),且HELLP组高于早发重度PE组(P均<0.05)。三组脐血HMGB1、RAGE蛋白水平相比,P均>0.05。结论 HMGB1、RAGE在早发重度PE及HELLP综合征患者胎盘组织及母血中的表达明显升高,二者可能共同参与了早发重度PE及HELLP综合征的发生发展过程。

Objective To observe the expression changes of high mobility group box 1 （ HMGB1 ） and receptor for ad- vanced gl yeation end products （RAGE） in the placenta, maternal serum and cord serum in patients with early-onset severe preeclampsia （PE） and HELLP syndrome, and to analyze the correlation of HMGBI and RAGE with the pathogenesis of ear- ly-onset severe PE and HELLP syndrome. Methods Thirty patients with early-onset severe preeclampsia （early-onset severe PE group）, 12 patients with HELLP syndrome （HELLP group） and 30 healthy pregnant women （control group） were recrui- ted in the study. Immunohistochemistry and Western blotting were used to investigate the locations and expression of HMGB1 and RAGE protein in the placentas. Real-time PCR was used to investigate the expression of HMGB1 and RAGE mRNA in the placentas. ELISA was further used to detect the levels of HMGB1 and RAGE protein in maternal and cord serums of the three groups. Results A low level of positive immunostaining for HMGB1 was observed in syncytiotrophoblast cells in pla- centas of control group, the level was significantly increased in syncytiotrophoblast and vascular endothelial cells in placentas of early-onset severe PE group, besides, in the placentas of HELLP group, positive HMGB1 ceils were mainly syncytiotropho- blast, macrophage and vascular endothelial cells. A small amount of positive immunostaining for RAGE was observed in syn- cytiotrophoblast and vascular endothelial cells in placentas of the control group, the distribution of positive cells in placentas of the early-onset severe PE group was consistent with that of the control group, what＇s more, in the placentas of HELLP group, the positive RAGE cells were mainly syncytiotrophoblast and macrophage cells （immunoreactive cells and the expres- sion intensity were significantly higher than those in the early-onset of severe PE group）. Compared with the control group, the protein and mRNA levels of HMGB1 and RAGE were increased in the placentas of early-onset PE and HELLP groups, furthermore, the levels of them in HELLP group were even higher than those in the early-onset severe PE group （ all P 〈 0.05）. In addition, the levels of HMGB1 and RAGE in the maternal serum of early-onset severe PE and HELLP groups were higher than those of the control group, besides, the levels of them in the HELLP group were even higher than those in the ear- ly-onset severe PE group （ all P 〈0.05 ）. However, there were no statistically significant differences in the levels of HMGB1 and RAGE in the cord serum among the three groups （ all P 〉0.05）. Conclusion The levels of HMGB1 and RAGE protein increase significantly in the maternal and cord serums of patients with early-onset severe PE and HELLP syndrome, both of which may participate the occurrence and development of early-onset severe PE and HELLP syndrome.