氧化低密度脂蛋白及其受体对滋养细胞凋亡的影响

目的:探讨氧化低密度脂蛋白(oxLDL)及血凝集素样氧化低密度脂蛋白受体1(LOX-1)对滋养细胞凋亡的影响。方法:采用蛋白印迹法检测滋养细胞LOX-1蛋白的表达;RT-PCR技术检测LOX-1mRNA及caspase-3mRNA的表达;流式细胞仪检测滋养细胞凋亡指数。结果:不同浓度oxLDL(0.01,0.05,0.10mg/ml)培养下细胞滋养细胞中LOX-1蛋白、mRNA及caspase-3mRNA表达水平均明显高于对照组(P<0.01),各组间比较差异均有统计学意义(P<0.01)。拮抗剂组LOX-1蛋白、mRNA及caspase-3mRNA表达水平均显著低于同浓度oxLDL刺激组,差异亦有统计学意义(P<0.01)。结论:oxLDL可通过上调滋养细胞中LOX-1表达引起滋养细胞的过度凋亡。     

Effects of oxidized low-density lipoprotein on leukocyte-endothelial interactions in the rat mesenteric microcirculation during pregnancy

OBJECTIVE: The accumulation of evidence implicates oxidized lipoproteins in atherosclerosis. Treatment of endothelial cells with these lipoproteins stimulates monocyte binding and the production of chemotactic factors that contribute to inflammation and endothelial injury and dysfunction. In preeclampsia, circulating low-density lipoprotein particles, which are susceptible to oxidation, are increased. We studied leukocyte-endothelial interactions that were related to oxidized lipoproteins in pregnant rats. STUDY DESIGN: We examined oxidized low-density lipoprotein-induced leukocyte behavior and uptake of fluorescent-labeled oxidized low-density lipoprotein in rat mesenteric venules during pregnancy, with the use of intravital microscopy with a video imager. RESULTS: The administration of oxidized low-density lipoprotein significantly reduced rolling velocities of leukocytes in venules and increased the numbers of leukocytes that adhered to endothelium in both nonpregnant and pregnant rats. These interactions were attenuated in pregnancy, when uptake of labeled oxidized low-density lipoprotein into leukocytes and endothelial cells also was decreased. CONCLUSION: Pregnancy may be associated with antioxidant effects.     

Autophagy protects against oxidized low density lipoprotein-mediated inflammation associated with preeclampsia

IntroductionInflammatory responses play an important role in the pathogenesis of preeclampsia. Recently, the anti-inflammatory role played by autophagy has drawn increasing attention. Our aim was to investigate variations in autophagy in preeclampsia and protection against oxidized low-density lipoprotein (oxLDL)-mediated inflammation by autophagy.MethodsWe used immunohistochemistry, immunofluorescence, quantitative real-time PCR, and western blotting to analyze the expression of autophagy proteins (beclin-1 and LC3II/LC3I) in preeclampsia placentas and in JEG-3 cells treated with oxLDL and rapamycin.ResultsWe found a decreased level of autophagy proteins in preeclampsia placentas, and oxLDL did not induce autophagy in JEG-3 cells. Furthermore, when cells were pretreated with rapamycin, autophagy was activated and expression of inflammatory factors (tumor necrosis factor-α and interleukin-6) induced by oxLDL was downregulated.ConclusionWe conclude that impaired autophagy in preeclampsia has potential to decrease trophoblast protection from oxidative and inflammatory stress, thereby contributing to the pathogenesis of preeclampsia.     

Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837 and r = -0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia.     

Decreased very-low-density lipoprotein and low-density lipoprotein receptor messenger ribonucleic acid expression in placentas from preeclamptic pregnancies

OBJECTIVE: Our purpose was to investigate the levels of very-low-density lipoprotein and low-density lipoprotein receptor messenger ribonucleic acid expression in placentas obtained from normal pregnant women at various gestational stages and from patients with preeclampsia. STUDY DESIGN: The relative level of expression of very-low-density lipoprotein and low-density lipoprotein receptor messenger ribonucleic acid in each sample was determined by Northern blot analysis as a ratio of the intensity to that of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid. RESULTS: The expression of very-low-density lipoprotein receptor messenger ribonucleic acid increased significantly (p < 0.05) from both the first (n = 9) and second (n = 8) trimesters to the third (n = 11) trimester. Similarly, the expression of low-density lipoprotein receptor messenger ribonucleic acid increased significantly (p < 0.05) from the first to the third trimester. The expression of both very-low-density lipoprotein and low-density lipoprotein receptor messenger ribonucleic acids in third-trimester placentas from preeclamptic pregnancies (n = 13) was significantly lower than that in normal pregnancies in the third trimester. CONCLUSION: These results demonstrate the expression of very-low-density lipoprotein and low-density lipoprotein receptor messenger ribonucleic acids in the human placenta, both of which increase at late gestational stages, and the decreased expression in cases of preeclampsia. Abnormal fetomaternal lipid metabolism resulting from low expression of these receptors in the placenta may be involved in the pathogenesis of preeclampsia. (Am J Obstet Gynecol 1996;175:1551-6.)     

子痫前期对氧磷酶1活性和代谢综合征变量变化的临床研究

目的:研究子痫前期患者血清对氧磷酶1(PON-1)活性及代谢综合征变量的变化和发生情况。方法:选择年龄、孕周、产次相匹配的轻度子痫前期患者38例(MPE组),重度子痫前期患者45例(SPE组),正常孕妇63例(对照组)为研究对象,测定其血清PON-1活性、丙二醛(MDA)、血脂及空腹血糖水平等指标。结果:子痫前期患者(MPE组+SPE组)血清MDA、总胆固醇、甘油三酯、低密度脂蛋白水平(LDL)均明显高于对照组(P<0.05),而血清PON-1活性及高密度脂蛋白(HDL)较对照组明显降低(P<0.05);SPE组空腹血糖较MPE组和对照组明显升高(P均<0.05)。子痫前期患者血清PON-1活性与MDA、甘油三酯、LDL水平呈负相关(P均<0.05),与HDL水平呈正相关(P<0.05),与BMI及空腹血糖无明显相关性(P>0.05)。对照组、MPE组及SPE组代谢综合征的发生率分别为3.2%,18.4%,33.3%。结论:子痫前期患者有代谢综合征的标志,推断两种疾病相互关联。子痫前期患者血清PON-1活性显著降低,可能为两种疾病相互关联的重要原因之一。     

Oxidized low-density lipoprotein and adiponectin levels in pregnancy

Introduction.?The aim of the present study was to investigate whether normal pregnancy represents a complex state of oxidative stress, inflammation and insulin resistance.

Subjects and methods.?One hundred and six pregnant women, between 24th and 28th week of pregnancy (age 27.9?±?0.4 years) (study group) and one hundred and six age-matched, healthy, non-pregnant women (control group) participated in the study. Serum levels of glucose, insulin, adiponectin, oxidized LDL (oxLDL) and lipid parameters, i.e. total cholesterol (TC), triglycerides (TG), HDL and LDL, were determined. Body mass index (BMI) and QUantitative Insulin sensitivity ChecK Index (QUICKI) were also calculated.

Results.?Pregnant women presented higher BMI values, insulin and oxLDL serum levels and lower glucose serum levels than controls. Serum levels of lipids (TC, TG, LDL and HDL) were higher in pregnant women. There was a significant positive correlation of oxLDL to adiponectin (p?<?0.01) in the study group, but not in the controls, and no other significant correlation with any of the other parameters, in either of groups.

Conclusions.?Pregnancy is a state of insulin resistance, oxidative stress and pro-atherogenic hyperlipidemia. Adiponectin may, though, have cardioprotective role in pregnant women.     

瘦素在子癎前期患者胎盘和血清的表达和意义

目的 探讨子癎前期患者胎盘和血清中瘦素的表达变化及其和子癎前期发病的关系.方法 采用免疫组化SP法检测45例子癎前期患者(研究组,其中重度组28例,轻度组17例)和30例同期正常妊娠妇女(对照组)胎盘瘦素水平,并用酶联免疫吸附实验检测两组孕妇产前血清瘦素水平.结果 (1)两组胎盘瘦素均在合体滋养细胞胞浆表达,随病情加重,染色逐渐加深,胎盘瘦素与子癎前期存在线性相关关系.(2)研究组、轻度组、重度组和对照组血清瘦素浓度分别为(10.41±4.78)ng/ml、(6.33±1.87)ng/ml、(12.88±4.27)ng/ml、(5.73±2.19)ng/ml,轻度组稍高于对照组但无统计学意义(P>0.05),研究组和对照组、轻和重度组、重度组和对照组相比,均有性统计学意义(P<0.01),瘦素表达水平和病情严重程度呈正相关.(3)血清瘦素与体重指数无相关性(P>0.05);但其与收缩压、舒张压及平均动脉压均呈正相关(r=0.602、0.566和0.585,P均<0.05).结论 瘦素在子癎前期患者胎盘和血清中均高表达,高瘦素水平参与子癎前期的发生和发展.     

子痫前期患者血脂代谢调节的探讨

目的:探讨子痫前期患者脂代谢调节水平及其异常调节情况。方法:采取前瞻性研究方法,随机抽取317例正常孕妇,分别测定不同妊娠周数的血脂和游离脂肪酸(FFA)水平;选取产前规律检查的正常孕妇54例,分别于孕10~14周,20~24周及30~34周测定血脂代谢水平。并随机抽取孕周相同、年龄相同或相近的正常孕妇77例与重度子痫前期77例进行1:1配对研究,比较血脂代谢变化。结果:正常妊娠妇女血清中TG、TCHO和LDL水平随妊娠周数增加而增加,但FFA和HDL水平并未随妊娠的周数的增加而发生明显变化。重度子痫前期TG和FFA水平较对照组明显升高(P<0.05),而HDL水平下降(P<0.05);FFA/HDL和LDL/HDL比值较对照组明显升高(P<0.05),而FFA/TG、FFA/LDL及FFA/TCHO比值无明显变化(P>0.05)。早发型重度子痫前期患者中肝功损害组的TCHO和LDL水平较对照组明显增高(P<0.05)。结论:重度子痫前期患者存在脂质代谢调节异常,具有损伤作用的FFA增加,而具有保护作用的HDL下降,FFA/HDL比值升高,重度子痫前期正常的血脂代谢平衡发生变化,FFA增加可能在重度子痫前期脂质代谢异常调节方面起到一定作用。     

Fetal gender,serum human chorionic gonadotropin,and testosterone in women with preeclampsia

ABSTRACT

Objectives

Evaluation of the association between fetal gender, serum beta-human chorionic gonadotropin, and serum testosterone, and preeclampsia.     

氧化低密度脂蛋白(ox-LDL)、白细胞介素(IL)-22在子痫前期患者血清及胎盘中的表达

目的:探讨血清及胎盘中氧化低密度脂蛋白(ox-LDL)、白细胞介素(IL)-22的表达与子痫前期(PE)发生的关系。方法:收集PE患者30例,其中轻度PE15例(轻度组),重度PE15例(重度组)。另选同期正常妊娠孕妇30例(正常组),分别采用ELISA、免疫组织化学方法检测血清、胎盘组织中ox-LDL、IL-22的表达水平。结果:1 PE轻度组和重度组患者血清及胎盘中ox-LDL水平均明显高于正常组(P0.05),且重度组明显高于轻度组(P0.05);2PE轻度组患者血清及胎盘中IL-22水平较正常组有升高趋势,但差异无统计学意义(P0.05),而重度组患者血清及胎盘中IL-22水平明显高于正常组及轻度组(P0.05);3 PE患者血清中ox-LDL与IL-22水平呈明显的正相关(r=0.941,P0.05);PE患者胎盘中ox-LDL与IL-22水平呈明显的正相关(r=0.754,P0.05)。结论:血清及胎盘中ox-LDL高表达可能与PE发生、发展有关,而IL-22在此过程中可能起到代偿性保护作用。     

Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low-density lipoprotein receptor 1 levels in early- and late-onset preeclampsia

Background

The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE).

Materials and methods

A case–control study was conducted in pregnant women with early-onset (before 34 weeks’ gestation n = 19) and late-onset (after 34 weeks’ gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels.

Results

The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age.

Conclusions

According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.     

广东籍汉族妇女N5,10-MTHFR基因和eNOS基因多态性与子痫前期和子痫相关性的研究

目的:探讨N5,10-亚甲基四氢叶酸还原酶(MTHFR)基因及内皮型一氧化氮合酶(eNOS)基因多态性与广东籍汉族妇女子痫前期和子痫发病的关系。方法:567例广东籍汉族妇女中54例诊断为子痫前期或子痫,513例为正常妊娠(对照组)。应用PCR-RFLP方法,检测567例早孕期妇女外周血MTHFR基因C677T突变和eNOS基因G894T突变,计算各基因型的相对风险率。结果:子痫前期和子痫组MTHFR C/C、C/T及T/T基因型频率分别为59.2%、20.4%及20.4%,其中T/T基因型频率显著高于对照组(5.5%)(P<0.001),并且T等位基因频率为30.6%,显著高于对照组(20.5%)(P<0.05),T/T基因型在子痫前期或子痫发病中的相对风险率为4.431。子痫前期和子痫组的eNOS基因频率与对照组无显著差异。结论:广东籍汉族妇女MTHFR基因C677T多态性可能与子痫前期或子痫发病的易感性相关,eNOS基因G894T多态性与子痫前期或子痫发病的易感性无关。     

Lack of association between the CYP11B2 gene polymorphism and preeclampsia, eclampsia, and the HELLP syndrome in Turkish women

OBJECTIVES: It is possible that altered control of aldosterone synthase gene (CYP11B2) expression or translation may be responsible for hypertension. Hypertension is one of the major components of preeclampsia. We present here a study investigating the association between the CYP11B2 gene polymorphism in the promoter region at the position of -344 and preeclampsia. STUDY DESIGN: We analyzed a group of Turkish women for preeclampsia (n=143), eclampsia (n=36), and the HELLP syndrome (n=55) and compared them with controls (n=147). Genotypes for CYP11B2 were determined by polymerase chain reaction followed by digestion with BsuRI restriction enzyme. RESULTS: The -344T/T, -344C/T, and -344C/C genotypes were found at comparable frequencies among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). We combined the genotypes of TC and CC (polymorphic) and compared them with the TT (wild-type) genotype. There was no significant difference in the frequency of the TC plus CC genotypes among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). There was no association of the CYP11B2 polymorphism among the preeclampsia, eclampsia, and HELLP groups and controls. CONCLUSIONS: The CYP11B2 gene polymorphism is not directly associated with preeclampsia, eclampsia, and the HELLP syndrome in women with these conditions. Therefore, this polymorphism may not be a risk factor for these disorders, at least not in the Turkish population.     

First trimester maternal characteristics,Doppler parameters and serum analytes after preeclampsia

Objective: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy. Methods: A total of 1283 parous patients were prospectively enrolled at 9–14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia. Results: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors. Conclusion: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.     

Auto antibodies against oxidized low density lipoprotein in severe preeclampsia

BACKGROUND: To study autoantibody titres against oxidized low density lipoprotein in preeclamsia. METHODS: Ten millimeters of heparinized blood samples were collected from 20 primigravidae with severe preeclamsia (study group) and 20 gestation-matched normotensive primigravidae (control group). Concentration of malondialdehyde, metabolite of lipid peroxidation were measured in sera by HPLC and autoantibodies against oxidized low density lipoproteins (obtained after oxidation with 2 mm CuSO(4)) were determined by ELISA. Statistical analysis was performed by Student's t-test and chi(2) test. RESULTS: Mean triglyceride levels were significantly (P < 0.001) higher in the study group (193.20 +/- 31.16 mg/dL) compared to the control group (170.60 +/- 23.2 mg/dL). Mean plasma lipid per oxide levels were not significantly different between the study (4.45 +/- 1.28 mmol/mL) and control (3.88 +/- 0.99 mmol/mL) groups. The majority of women in both groups had low antibody titres (<1.32) against low density lipoprotein. Six women (30%) of the study group and four (20%) of the control group had high autoantibody titres (>/=1.32). In preeclamptic women, diastolic blood pressure, the amount of urinary protein excretion and the plasma level of urea were significantly higher (P < 0.05) in patients with higher auto antibody titre. CONCLUSION: Titres of autoantibodies to oxidized low density lipoprotein were similar in normotensive and preeclamptic women. In preeclamptic women, titres correlated positively with the severity of preeclampsia.     

Maternal serum autotaxin levels in early- and late-onset preeclampsia

Purpose: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital.

Methods: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients.

Results: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels.

Conclusion: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.