ABSTRACT
Objective 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 preeclampsia.Methods Fifteen early-onset pre-eclaraptic 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-peroxidose method.Results (1)Immunoreactivities to HMGB1:positive immnnostaining 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).Conclusions The increased expression of HMGB1 and RACE in the placenta may play an important role in the pathogenesis of pre-eclampsis.The different locations may be associated with the occurrence of different onset types of pre-eclampsia.
ABSTRACT
Objective To investigate the role of hypoxia inducible factor(HIF)-prolyl hydroxylase 1 (HPHl)and factor inhibiting HIF-1(FIH-1)in placentas in the pathogenesis and development of severe pre-eclampsia.Methods RT-PCR and western blot analyses were used to detect the HPH1 and FIH-1expression levels in placentas of 34 patients with severe pre-eclampsia and 24 cases of term pregnancy (normal pregnancy group)and their correlations with symptoms were analyzed.Results (1)The HPHI mRNA and protein expression levels in placentas of severe pre-eclampsia group were 0.40±0.04 and 59.5±3.4 separately,significantly lower than those of normal pregnancy group,0.84±0.12 and 71.6±1.7(P<0.01).The FIH-1 mRNA and protein expression levels in placentas of severe pre-eclampsia group wereQ 31 ±0.05 and 45.6±2.4 separately,significantly lower than those of normal pregnancy group,0.43±0.04 and 54.9±2.1(P<0.01).(2)The mRNA and protein expression levels of HPH1 and FIH-1 in severe pre-eclampsia group were all negatively correlated with mean arterial pressure(MAP)[the Spearman correlation coefficient was-0.854(P<0.01)],urinary protein per 24 hours[the Spearman correlation coefficient was-0.936(P<0.01)1 and the occurrence of fundus oculi artery spasm[the Spearman correlation coefficient was-0.854(P<0.01)].(3)rrhe expression of HPHl mRNA in placentas of all the 58 cases WBB 0.58±0.27.higher than the expression of FIH-1 mRNA,which was 0.39±0.10.There was a positive correlation between them.The pearson correlation coefficient was 0.686(P<0.01).The expression of HPH1 protein in placentas of all the 58 cases was 64.5±6.7,higher than the expression of FIH-1,which was 49.4±5.2.There was a positive correlation between them.The Pearson correlation coefficient was 0.947(P<0.01).Conclusion The expression imbalance of HPH1 and FIH-1in palcenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1a.