Molvarec Attila, Rigó János, Lázár Levente, Balogh Krisztián, Makó Veronika, Cervenak László, Mézes Miklós, Prohászka Zoltán
1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Cell Stress Chaperones. 2009 Mar;14(2):151-9. doi: 10.1007/s12192-008-0067-8. Epub 2008 Aug 7.
It has been previously reported that serum levels of 70-kDa heat-shock protein (Hsp70) are elevated in preeclampsia. The aim of the present study was to examine whether increased serum Hsp70 levels are related to clinical characteristics and standard laboratory parameters of preeclamptic patients, as well as to markers of inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) or endothelial injury (fibronectin), trophoblast debris (cell-free fetal DNA) and oxidative stress (malondialdehyde). Sixty-seven preeclamptic patients and 70 normotensive, healthy pregnant women were involved in this case-control study. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Standard laboratory parameters (clinical chemistry) and C-reactive protein (CRP) levels were determined by an autoanalyzer using the manufacturer's kits. Plasma von Willebrand factor antigen (VWF:Ag) levels were quantified by ELISA, and plasma fibronectin concentration by nephelometry. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time polymerase chain reaction analysis of the sex-determining region Y gene. Plasma malondialdehyde levels were measured by the thiobarbituric acid-based colorimetric assay. Serum Hsp70 levels were increased in preeclampsia. Furthermore, serum levels of blood urea nitrogen, creatinine, bilirubin and CRP, serum alanine aminotransferase and lactate dehydrogenase (LDH) activities, as well as plasma levels of VWF:Ag, fibronectin, cell-free fetal DNA and malondialdehyde were also significantly higher in preeclamptic patients than in normotensive, healthy pregnant women. In preeclamptic patients, serum Hsp70 levels showed significant correlations with serum CRP levels (Spearman R = 0.32, p = 0.010), serum aspartate aminotransferase (R = 0.32, p = 0.008) and LDH activities (R = 0.50, p < 0.001), as well as with plasma malondialdehyde levels (R = 0.25, p = 0.043). However, there was no other relationship between serum Hsp70 levels and clinical characteristics (age, parity, body mass index, blood pressure, gestational age, fetal birth weight) and laboratory parameters of preeclamptic patients, including markers of endothelial activation or injury and trophoblast debris. In conclusion, increased serum Hsp70 levels seem to reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Nevertheless, further studies are required to determine whether circulating Hsp70 plays a causative role in the pathogenesis of the disease.
先前已有报道称,子痫前期患者血清中70-kDa热休克蛋白(Hsp70)水平升高。本研究的目的是检验血清Hsp70水平升高是否与子痫前期患者的临床特征、标准实验室参数,以及炎症标志物(C反应蛋白)、内皮激活标志物(血管性血友病因子抗原)或内皮损伤标志物(纤连蛋白)、滋养层碎片(游离胎儿DNA)和氧化应激(丙二醛)有关。67例子痫前期患者和70例血压正常的健康孕妇参与了这项病例对照研究。采用酶联免疫吸附测定法(ELISA)检测血清Hsp70水平。使用制造商提供的试剂盒,通过自动分析仪测定标准实验室参数(临床化学指标)和C反应蛋白(CRP)水平。采用ELISA法定量检测血浆血管性血友病因子抗原(VWF:Ag)水平,采用散射比浊法检测血浆纤连蛋白浓度。通过对性别决定区Y基因进行定量实时聚合酶链反应分析,测定母体血浆中游离胎儿DNA的含量。采用基于硫代巴比妥酸的比色法检测血浆丙二醛水平。子痫前期患者血清Hsp70水平升高。此外,子痫前期患者血清中的尿素氮、肌酐、胆红素和CRP水平、血清丙氨酸转氨酶和乳酸脱氢酶(LDH)活性,以及血浆中的VWF:Ag、纤连蛋白、游离胎儿DNA和丙二醛水平也显著高于血压正常的健康孕妇。在子痫前期患者中,血清Hsp70水平与血清CRP水平(Spearman相关系数R = 0.32,p = 0.010)、血清天冬氨酸转氨酶(R = 0.32,p = 0.008)和LDH活性(R = 0.50,p < 0.001),以及血浆丙二醛水平(R = 0.25,p = 0.043)均呈显著相关。然而,血清Hsp70水平与子痫前期患者的临床特征(年龄、产次、体重指数、血压、孕周、胎儿出生体重)和实验室参数,包括内皮激活或损伤标志物以及滋养层碎片之间没有其他关联。总之,血清Hsp70水平升高似乎反映了子痫前期患者的全身炎症、氧化应激和肝细胞损伤。然而,还需要进一步研究以确定循环Hsp70在该疾病发病机制中是否起致病作用。