Dysferlin在子痫前期发病机制中的研究

子痫前期是一种严重的妊娠并发症,发病率约为2％-8％,是孕产妇和围产儿发病及死亡的主要原因之一,严重威胁母婴健康,然而其病因和发病机制至今尚未完全阐明.有研究表明,胎盘在子痫前期的发生中是一个关键.在整个孕期,母婴物质交换位于胎盘的合体滋养层顶端质膜,同时,免疫和细胞修复也发生于此[1].因此在胎盘滋养细胞中寻找与子痫前期相关基因成为病因研究的热点.Dysferlin是人体内一种与细胞膜自身修复有关的跨膜蛋白,在骨骼肌膜修复过程中起着重要作用[2].近期有研究表明,Dysferlin也参与了合体滋养细胞的质膜修复.本文就Dysferlin在子痫前期发病机制作一综述.     

对氧磷酶的某些研究进展

对氧磷酶 (PON)多基因家族至少有 3个成员 ,包括PON1、PON2和PON3。PON1是PON多基因家族中发现最早 ,研究最多的成员 ,其基因产物血清对氧磷酶在有机磷神经毒剂解毒中起重要作用 ,其基因多态性与脑卒中、动脉粥样硬化、冠心病及 2型糖尿病发病等有密切关系 ;PON2基因多态性与家族性高胆固醇血症、糖尿病等有关 ;PON3基因产物目前尚未有在人体组织中存在的报道 ,它们的生理作用仍在探索中。现将PON研究的进展综述如下。1　PON多基因家族PON多基因家族至少存在 3个成员 :PON1、PON2、PON3,它们位于人类 7号染色体的长臂q2 1 …     

子痫前期患者胎盘早剥发病危险因素分析

目的：分析子痫前期患者胎盘早剥发病的危险因素,为临床子痫前期患者的诊断和治疗提供依据。方法将本院收治的子痫前期患者259例按是否合并胎盘早剥分为观察组和对照组,进行胎盘早剥发病危险因素的单因素及多因素Logistic回归分析。结果单因素分析结果显示,孕周、分娩史、纤维蛋白原、尿素氮、肌酐和间接胆红素差异有统计学意义;多因素logistic回归分析显示分娩史、纤维蛋白原和肌酐是导致子痫前期胎盘早剥产生的重要因素。结论血浆纤维蛋白原含量过低、肌酐水平偏高、有多产史的子痫前期孕妇发生胎盘早剥的几率高,应有针对性地进行干预,改善妊娠结局。     

硝酸甘油在重度子痫前期及子痫的应用

妊娠期高血压疾病（HDCP）是产科最常见的并发症,可伴全身多器官功能损害或功能衰竭;该病严重威胁母婴健康,是导致孕产妇和围产儿病率和死亡的重要原因之一[1]。按第7版人民卫生出版社出版的五年制、八年制医学院校妇产科学教材标准分期,分为妊娠期高血压、子痫前期（轻、重）、子痫、妊娠合并慢性高血压、慢性高血压并发子痫前期。     

子痫前期及子痫患者血清中超敏 C-反应蛋白水平探讨

目的：研究子痫前期及子痫患者血清中超敏C-反应蛋白的水平，探讨超敏C-反应蛋白与子痫疾病发生发展的关系。方法自2011年2月至2012年12月期间进行产前检查的1473例孕妇中随机抽选176例作为研究对象，并根据孕妇健康检查状况进行分组，分为子痫组52例、子痫前期组70例、正常孕妇组54例。通过定量监测的方法检测他们体内的超敏C-反应蛋白，记录其监测结果并进行综合评价。结果子痫前期组超敏C-反应蛋白的值明显高于正常孕妇组（ P ＜0湝．05）；子痫组超敏C-反应蛋白的值明显高于子痫前期组（ P ＜0．05）；子痫前期组中重度患者超敏C-反应蛋白的值明显高于子痫前期组中轻度患者（ P ＜0．05）；子痫组中伴有其他并发症的患者超敏C-反应蛋白的值明显高于不伴有其他并发症的患者（ P ＜0．05）。结论超敏C-反应蛋白与子痫联系密切，而且随着病情的轻重而成正相关的变化，临床上可以用于此类疾病的早期筛查，并可以根据检测指标的大小评估子痫的发展情况，为疾病的早期治疗打下良好的基础。     

对氧磷酶2研究进展

<正>对氧磷酶(paraoxonase,PON)基因家族包含3个高度保守的基因:PON1基因、PON2基因与PON3基因,它们都位于染色体7q21.3-22.1区域,三者具有高度的同源性。由于PON2独特的表达特性和分布特性,近年来的研究热点聚焦于此。与PON1和PON3不同,PON2在人体的诸多组织具有表达,包括:肝脏、肾脏、肺脏、心脏、胎盘、睾丸、胃、脾脏、胰腺、小肠、骨骼肌、动脉壁细胞以及巨噬细胞。尽管PON2具有与PON1高度同源的氨基酸序列和相似的结     

心脏X综合征患者血清对氧磷酶-1变化及意义

目的探讨心脏X综合征时血清对氧磷酶-1（PON-1）水平的变化及其在心脏X综合征发病机制中的作用。方法将心内科患者60例,分为心脏X综合征（CSX）组30例、非心脏X综合征（NCSX）组30例和正常对照组30例。采用分光光度法检测血清PON-1的活性。结果CSX患者血清PON-1活性较NCSX组和对照组降低（P〈0.01）,血清PON-1活性与低密度脂蛋白（LDL）水平呈负相关（P〈0.01）。结论血清PON-1活性降低参与了心脏X综合征的发生。     

重度子痫前期子痫对母婴影响40例临床分析

目的：分析与研究重度子痫前期子痫对母婴产生的影响。方法40例重度子痫前期子痫产妇作为研究组，治疗以镇静、解痉以及降压为主；选取同期40例健康的产妇作为对照组进行对比，对比两组产妇围生儿的预后情况。结果研究组产妇并发症发生率75%、围生儿预后不良发生率32.5%明显高于对照组40%、7.5%，两组比较差异具有统计学意义（P〈0.05）。结论重度子痫前期子痫对于母婴预后有着严重的影响，预防重度子痫前期子痫的发生十分重要。     

基于生物信息学分析miR-152在子痫前期发病机制中的作用

目的 分析子痫前期（preeclampsia,PE）相关差异表达miRNAs,选择miR-152预测其靶基因并进行生物信息学分析,探讨其参与子痫前期发病的分子机制。方法 于GEO数据库中选择子痫前期胎盘组织miRNA差异表达数据集GSE103542,选择上调最显著的miR-152作为研究对象,应用miRDB、TargetScan及miRTarBase软件预测其靶基因并取交集;利用DAVID网络在线富集工具对交集靶基因进行GO功能注释及KEGG通路富集分析,并利用STRING网站对其进行蛋白质互作分析。结果 获得的418个交集靶基因在生物过程（biological process,BP）上主要涉及生物黏附、细胞黏附及细胞发育调控等;在细胞组成（cellular component,CC）上主要涉及质膜组成部分、网格蛋白囊泡等;在分子功能（molecular function,MF）上主要涉及钙离子结合、离子结合等。KEGG信号通路富集分析显示其主要参与了调控干细胞多能性的信号通路及TGF-信号通路。蛋白互作分析显示IGF1R、SMAD3、RPS6KB1及PPP2CA是蛋白互作网络的关键节...     

联合用药对子痫前期的预防作用

目的探讨联合应用小剂量阿司匹林、维生素E、乐力钙在预防子痫前期发病中的作用。方法选择子痫前期高危孕妇46例,将其随机分为治疗组及对照组各23例,治疗组每日给予阿司匹林75mg、维生素E100mg、乐力钙2．0g口服,至分娩。对照组按常规处理。结果无论是轻度或重度子痫前期,治疗组的发病率（13．0％）均显著低于对照组（39．1％）（P〈0．05）;治疗组早产率、死胎率及新生儿窒息发生率均显著低于对照组（P〈0．05）,而产后出血及胎盘早剥发生率在两组间无显著差异（P〉0．05）。结论联合应用小剂量阿司匹林、维生素E、乐力钙对子痫前期的发生有着重要的预防价值。     

High-dose taurine supplementation increases serum paraoxonase and arylesterase activities in experimental hypothyroidism

1. Hypothyroidism is accompanied by hyperlipidaemia and oxidative stress and is associated with several complications, such as atherosclerosis. Paraoxonase activity has been reported to decrease in several situations associated with atherosclerosis and oxidative stress. In the present study, the effects of different doses of taurine on serum paraoxonase and arylesterase activities, as well as on the serum lipid profile, were investigated in hypothyroid rats. 2. Forty male Sprague-Dawley rats were randomly divided into five groups as follows: Group 1, rats received normal rat chow and tap water; Group 2, rats received standard rat chow + 0.05% propylthiouracil (PTU) in the drinking water; and Groups 3-5, taurine-supplemented PTU groups (standard rat chow + 0.5, 2 or 3% taurine in the drinking water, respectively, in addition to PTU). Paraoxon or phenylacetate were used as substrates to measure paraoxonase and arylesterase activity, respectively. Plasma and tissue malondialdehyde (MDA) levels, indicators of lipid peroxidation, were determined using the thiobarbituric-acid reactive substances method. Serum triglyceride, total cholesterol and high-density lipoprotein-cholesterol (following precipitation with dextran sulphate-magnesium chloride) were determined using enzymatic methods. 3. Serum paraoxonase and arylesterase activities were increased and plasma and tissue MDA levels and serum triglyceride levels were reduced in a dose-dependent manner in taurine-treated hypothyroid rats. Taurine concentrations were positively correlated with enzyme activities and negatively correlated with MDA and triglyceride levels. 4. Further studies are needed to investigate the role of taurine supplementation in hypothyroidism in human subjects.     

分光光度法与荧光法测定肝组织丙二醛含量的比较研究

目的比较分光光度法与荧光法测定肝组织MDA的结果,探讨最适合测定肝组织MDA含量的方法。方法通过两种方法所建立的标准曲线计算大鼠肝组织中MDA含量及体外FeSO4诱导肝匀浆生成的MDA量,采用荧光法测定灯盏花素体外对FeSO4诱导肝组织生成MDA含量的影响。结果分光光度法测定肝组织MDA含量及体外FeSO4诱导MDA含量的△A值均在标准曲线最低测定值0.1以下,而荧光法测定值均在其标准曲线最低测定值0.4以上。灯盏花素终浓度在1.02～11.25mg·mL-1可抑制FeSO4诱导的肝组织生成MDA,且有一定的量效关系。结论由于肝匀浆本底的干扰,采用分光光度法往往难于通过其标准曲线计算出MDA准确含量,不适合用于肝组织的测定。建议采用荧光法替代。     

有机磷对作业工人红细胞乙酰胆碱酯酶和血清对氧磷酶活力的影响

目的探讨接触有机磷对作业工人红细胞乙酰胆碱酯酶(eAChE)和血清对氧磷酶(sPON)活力的影响。方法采用GC-NPD(气相色谱-氮磷检测器)监测作业场所空气中有机磷农药浓度,试剂盒和标准曲线法测定作业工人和对照者eAChE和sPON活力。结果对硫磷包装车间呼吸带的浓度为(0.022±0.012)mg/m3,敌敌畏包装车间呼吸带的浓度为(1.960±1.180)mg/m3;有机磷暴露使作业工人的eAChE及sPON活力降低并与接触工龄呈负相关;对硫磷暴露组中≥35岁作业工人的eAChE活力高于<35岁的作业工人,饮酒可以降低eAChE活力而升高sPON活力。结论eAChE及sPON活力可以作为评价有机磷农药中毒程度的生物标志物。     

电焊工人血清超氧化物歧化酶及丙二醛分析

目的　探讨电焊作业人员对机体脂质过氧化及抗氧化水平的影响。方法　选择 67名电焊作业人员及 5 6名对照人员 ,测定其血清超氧化物岐化酶 (SOD)活性及丙二醛 (MDA)含量。结果　电焊作业人员血清SOD活性低于对照组 ,MDA含量高于对照组 ,差异有显著意义。结论　电焊作业人员接触较高浓度锰及其化合物 ,后者使机体脂质过氧化及抗氧化功能紊乱。     

早发型与晚发型重度子痫前期临床生化指标比较

目的对比早发型与晚发型子痫前期临床生化指标,为抗凝治疗提供依据。方法选取子痫前期患者220例,以孕龄34周为界,分为早发型包括轻度40例(A组),重度60例(B组),与晚发型轻度60例(C组),重度60例(D组),对比4组凝血纤溶指标,血浆同型半胱氨酸,血脂的差异。结果早发型重度子痫前期血凝血酶原时间(PT),活化部分凝血酶原时间(APTT)均缩短,血小板计数(PLT)下降,而纤维蛋白原(Fg)、D-二聚体(DD)、组织纤溶酶原激活物(t-PA)、组织纤溶酶原激活物抑制剂(PAI-1)均升高,血浆同型半胱氨酸升高,与晚发型对比,2组差异有统计学意义(P<0.05)。早发型重度子痫前期患者总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、载脂蛋血B(apoB)明显高于晚发组;而HDL、apoA低于晚发组,2组差异有统计学意义(P<0.05);结论早发型重度子痫前期患者存在高脂血症,高同型半胱氨酸血症,处于过高凝状态,抗凝治疗很有必要。     

42例子痫前期患者血清学指标与尿蛋白值变化及其临床意义

目的：探讨子痫前期血清学指标与尿蛋白值变化及其临床意义。方法：选取我院产科子痫前期孕妇42例作为研究组,同期选取正常孕妇40例作为对照组,采用ELISA方法检测血清AST、ALT、GGT、TP、ALB、Urea、Cr、UA、b2-MG、LDH和24 h电泳检测尿蛋白UPRO,比较两组上述指标的差异。结果：研究组血清学指标（AST、ALT、GGT、Urea、Cr、UA、b2-MG、LDH）和尿蛋白值均明显高于对照组,血清TP、ALB均明显低于对照组,两组比较均有显著性差异。结论：上述指标可能参与子痫前期病情的发生。     

子痫前期患者脂质过氧化及抗氧化水平的变化

目的 评价子痫前期患者与正常孕妇的脂质过氧化和抗氧化状态的变化.方法 68例女性,年龄23～35岁,分为3组.A组23例为血压正常孕妇,孕期28～39周.B组26例为子痫前期孕妇,孕期28～39周.C组19例为血压正常的健康未孕女性.所有女性均检测血浆丙二醛(MDA)水平来评价机体的脂质过氧化、血浆抗氧化酶超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶、过氧化氢酶以及抗氧化物还原型谷胱甘肽(GSH)和维生素C的水平.结果 B组脂质过氧化水平明显增高.与C组相比A组和B组GSH水平均明显降低而SOD水平均明显升高(P<0.01).与C组相比,A组血浆过氧化氢酶、谷胱甘肽过氧化酶等抗氧化酶水平明显降低(P<0.01).作为抗氧化物的维生素C的水平,与A组和C组比较B组明显升高(P<0.01).结论 机体的先天性抗氧化系统可以对抗子痫前期诱发的氧化应激反应.     

The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters

Aims

Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters.

Methods

One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day⁻¹ atorvastatin, 10/20 mg day⁻¹ simvastatin and 80 mg day⁻¹ extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method.

Results

Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group.

Conclusions

The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• It has been suggested that the human paraoxonase-1 (PON1) genotype is an important determinant of the therapeutic response given to statin treatment.
• It is also known that the PON1 activity status is a better predictor of coronary heart disease risk than any of the known PON1 genotypes.
• Our goal was to answer this previously uninvestigated, still clinically relevant question: does the PON1 phenotype have an impact on the paraoxonase-activating and lipid-lowering effect of different types of statins.

WHAT THIS STUDY ADDS

• All the statins (atorvastatin, simvastatin and fluvastatin) included in this study were able to increase serum paraoxonase activity and decrease triglyceride levels effectively; however, this response seemed to be more significant in patients with AB+BB PON1 phenotype than in those bearing AA PON1 phenotype.
• Furthermore, the apolipoprotein B-lowering effect of atorvastatin was also found to be PON1 phenotype-dependent.
• Our results indicate that the PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.

     

Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type 2 diabetic patients

1. In the present study, we have explored the effect of rosiglitazone on post-prandial paraoxonase (PON)-1, an enzyme with potent anti-oxidant properties that may protect against atherosclerosis because increased post-prandial lipaemia, although sometimes understated, is part of the diabetic dyslipidaemia. 2. A randomized, cross-over, placebo-controlled, double-blind clinical trial was performed. Participants (19 type 2 diabetic patients on oral antihyperglycaemic agents) were randomly assigned to receive either placebo or rosiglitazone 4 mg twice daily for 8 weeks. After a 6 week wash-out, the alternative treatment was implemented. Standardized 6 h oral fat-loading tests were performed after each treatment period. 3. Patients assigned to rosiglitazone had increased fasting PON-1 activity (from 331 +/- 29 to 362 +/- 32 U/L before treatment vs after treatment, respectively; P = 0.015), although the PON-1 mass did not change (68.8 +/- 21.1 vs 64.2 +/- 25.4 mg/L before treatment vs after treatment, respectively). In addition, rosiglitazone significantly decreased fasting plasma peroxides compared with placebo (162 +/- 25 vs 214 +/- 28 mmol/L, respectively; P = 0.019). The post-prandial fall in PON-1 activity, expressed as area under the curve, was attenuated by rosiglitazone (-97 +/- 14 vs-161 +/- 24 Uh/L for rosiglitazone vs placebo, respectively; P = 0.02) and the increase in PON-1 activity caused by rosiglitazone correlated with reductions in fasting plasma glucose (r = -0.42; P < 0.05), homeostatic model assessment index (r = -0.59; P < 0.01) and peroxides (r = -0.40; P = 0.07). 4. The present data indicate that rosiglitazone may convey increased protection against the oxidative modification that represents increased post-prandial lipaemia.     

Variability of the paraoxonase gene (PON1) in Euro- and Afro-Brazilians

The human high-density lipoprotein-associated paraoxonase (EC 3.1.1.2; PON1) plays a role in the hydrolysis of organophosphorus compounds and against the oxidative damage of low-density lipoprotein. In the present study, variants of PON1 (55 and 192) were investigated by PCR-RFLP and PCR-SSCA in Euro- (N = 101) and Afro-Brazilians (N = 70). The PON1*55 and PON1*192 allele frequencies were significantly different in these ethnic groups (p < 0.05 and p < 0.001, respectively). The genotype frequencies for PON1*55 (LL, LM, and MM) in Euro- and Afro-Brazilians were 33, 56, and 11% and 47, 49, and 4%, respectively. The genotype frequencies for PON1*192 were significantly different in Euro- and Afro-Brazilians (QQ, QR, RR: 48, 42, and 10% and 21, 52, and 27%, respectively; p < 0.001). The haplotype frequency distributions were also significantly different in Euro- (LQ = 30.20%; LR = 30.69%; and MQ = 39.11%) and Afro-Brazilians (LQ = 24.97%; LR = 46.46%; MQ = 22.18%; and MR = 6.39%; p < 0.001). Linkage disequilibrium (D) in relation to the maximum expected value was higher in Euro- (100%) than in Afro-Brazilians (58%). We suggest that the high linkage disequilibrium in Caucasians and Asians characterized by the absence or very low frequency of the MR haplotype is mainly due to genetic drift and possibly also to natural selection favoring the PON1*192Q allele or a variant in linkage disequilibrium with it. This seems to be the first study on the PON1 variability at the DNA level in South American samples and one of the few studies on individuals of mixed African origin.