CN114470161A - 骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 - Google Patents
骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 Download PDFInfo
- Publication number
- CN114470161A CN114470161A CN202210073640.XA CN202210073640A CN114470161A CN 114470161 A CN114470161 A CN 114470161A CN 202210073640 A CN202210073640 A CN 202210073640A CN 114470161 A CN114470161 A CN 114470161A
- Authority
- CN
- China
- Prior art keywords
- preeclampsia
- bmp6
- early
- diagnosis
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 201000011461 pre-eclampsia Diseases 0.000 title claims abstract description 65
- 238000013399 early diagnosis Methods 0.000 title claims abstract description 15
- 230000002265 prevention Effects 0.000 title claims description 7
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 title abstract description 9
- 102000008154 Bone Morphogenetic Protein 6 Human genes 0.000 title description 8
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 claims abstract description 43
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 claims abstract description 42
- 108010082093 Placenta Growth Factor Proteins 0.000 claims abstract description 19
- 102100035194 Placenta growth factor Human genes 0.000 claims abstract description 19
- 238000003745 diagnosis Methods 0.000 claims abstract description 17
- 210000002993 trophoblast Anatomy 0.000 claims abstract description 15
- 108010023082 activin A Proteins 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000003550 marker Substances 0.000 claims abstract description 9
- 208000032594 Vascular Remodeling Diseases 0.000 claims abstract description 7
- 230000003169 placental effect Effects 0.000 claims abstract description 7
- 238000011161 development Methods 0.000 claims abstract description 5
- 230000003511 endothelial effect Effects 0.000 claims abstract description 5
- 230000009545 invasion Effects 0.000 claims abstract description 4
- 108010059616 Activins Proteins 0.000 claims description 7
- 102100026818 Inhibin beta E chain Human genes 0.000 claims description 7
- 239000000488 activin Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000003449 preventive effect Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 2
- 210000002966 serum Anatomy 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 15
- 230000035935 pregnancy Effects 0.000 description 10
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 210000002826 placenta Anatomy 0.000 description 6
- 239000003102 growth factor Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000035488 systolic blood pressure Effects 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 230000008774 maternal effect Effects 0.000 description 4
- 108010082117 matrigel Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 238000008157 ELISA kit Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- -1 sEndoglin Proteins 0.000 description 3
- 101150118536 HTR8 gene Proteins 0.000 description 2
- 101100297639 Mus musculus Pigf gene Proteins 0.000 description 2
- 238000010220 Pearson correlation analysis Methods 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 102000046095 human BMP6 Human genes 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010070538 Gestational hypertension Diseases 0.000 description 1
- 201000005624 HELLP Syndrome Diseases 0.000 description 1
- 208000005347 Pregnancy-Induced Hypertension Diseases 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 208000036335 preeclampsia/eclampsia 1 Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/36—Gynecology or obstetrics
- G01N2800/368—Pregnancy complicated by disease or abnormalities of pregnancy, e.g. preeclampsia, preterm labour
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Reproductive Health (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
本发明涉及生物医药技术领域，具体涉及骨形态发生蛋白6在子痫前期早期诊断及治疗中的应用。本发明提供BMP6作为子痫前期早期诊断/治疗标志物的应用，BMP6联合PlGF和激活素A在子痫前期早期诊断中的应用，以及BMP6在制备子痫前期预防和治疗药物的应用。本发明发现了BMP6联合PlGF和激活素A在子痫前期早期诊断中可提高现有诊断标记物对子痫前期诊断效果；并且还发现了BMP6能够增加人滋养层细胞的侵袭力和内皮特性获得，改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，继而改善子痫前期的发展，具有制备子痫前期预防和治疗药物的潜力。
Description
技术领域
本发明涉及生物医药技术领域，具体涉及骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用。
背景技术
公开该背景技术部分的信息仅仅旨在增加对本发明的总体背景的理解，而不必然被视为承认或以任何形式暗示该信息构成已经成为本领域一般技术人员所公知的现有技术。
子痫前期是常见的妊娠相关疾病，是导致孕产妇和新生儿发病及死亡的主要原因之一。由于子痫前期的病因和发病机制复杂，目前临床诊疗中尚缺乏除对症治疗外的有效靶标治疗药物，多数患者不得不接受提前终止妊娠的手术治疗。此外，早期诊断和识别子痫前期患者可帮助临床医生提前发现高危人群并对子痫前期患者进行早期管理和治疗，阻止病情恶化，降低不良孕产结局发生率。但是，目前尚无针对子痫前期早期诊断治疗的有效靶标。因此，深入阐明发病机制并筛查有效的诊疗潜在靶点分子对于子痫前期的诊断和干预尤为必要。
胎盘分泌的生长因子可在母胎界面对胎盘发育过程中滋养层细胞分化和功能起关键调控作用，被认为可以作为子痫前期早期预测及治疗的潜在靶标。此外，胎盘分泌的生长因子可以进入母体血液循环，其在母体妊娠期血液中的表达水平陆续被认为能够反映胎盘发育情况，并有望成为子痫前期发生的早期预测诊断靶标分子。已有研究提出可通过检测妊娠早期孕妇外周血血清中激活素A, sEndoglin,PlGF,sFLT-1,VEGF等胎盘分泌生长因子的表达水平来预测子痫前期的发病风险。但上述已知的标记分子预测子痫前期的特异性和准确性仍有待进一步证实，且妊娠母体血清中sFLT-1, PlGF，sEndoglin，激活素A，sFLT1:PlGF表达水平变化往往伴随疾病症状的迅速出现，无法在妊娠早期(如妊娠11-12周)对子痫前期的发生进行预警和诊断。因此，发掘妊娠早期母体外周血中新的与子痫前期相关的关键胎盘分泌因子，筛选敏感有效的生物标志物，对于子痫前期的早期诊断、早期干预尤为必要。
发明内容
针对现有技术中存在的问题，本发明的目的是提供一种骨形态发生蛋白6(BMP6)在子痫前期早期诊断、预防及治疗中的应用，提供BMP6联合PlGF和激活素A在子痫前期早期诊断中的应用，提高现有诊断标记物对子痫前期诊断效果；并且还发现了BMP6具有预防及治疗子痫前期治疗的潜力。
为了实现上述目的，本发明的技术方案如下所述：
在本发明的第一方面，提供骨形态发生蛋白6(BMP6)作为子痫前期早期诊断/预防/治疗标志物的应用。
在本发明的第二方面，提供骨形态发生蛋白6(BMP6)联合PlGF和激活素A在子痫前期早期诊断中的应用；
BMP6联合PlGF、激活素A可提高现有诊断标记物对子痫前期诊断效果(AUC：0.943)。BMP6 联合PlGF、激活素A诊断与患者收缩压(SBP)和肌酐水平正相关(P<0.05)。
在本发明的第三方面，提供一种子痫前期诊断试剂盒，所述诊断试剂盒中包括检测BMP6、PlGF 和激活素A表达含量的试剂。
在本发明的第四方面，提供一种骨形态发生蛋白6(BMP6)在制备子痫前期预防/治疗药物的应用；
所述预防/治疗药物的作用包括：
增加人滋养层细胞的侵袭力和内皮特性获得；
预防子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，继而预防子痫前期的发生，降低子痫前期的发生风险。
在本发明的第五方面，提供一种子痫前期预防/治疗方法，所述预防/治疗方法包括改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，减轻子痫前期患者妊娠期高血压、蛋白尿症状的严重程度。
在本发明的第六方面，提供一种子痫前期的预防/治疗药物，所述药物以骨形态发生蛋白6 (BMP6)作为活性物质。
本发明的具体实施方式具有以下有益效果：
本发明提供BMP6作为子痫前期早期诊断/治疗标志物的应用，发现了BMP6联合PlGF和激活素A在子痫前期早期诊断中可提高现有诊断标记物对子痫前期诊断效果；并且还发现了BMP6能够增加人滋养层细胞的侵袭力和内皮特性获得，改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，继而改善子痫前期的进展，具有制备子痫前期预防及治疗药物的潜力。
附图说明
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解，本发明的示意性实施例及其说明用于解释本发明，并不构成对本发明的不当限定。
图1：A上图：ELISA检测正常和子痫前期孕妇血清中BMP6、水平(N为41vs.26)；下图： ROC曲线显示血清中BMP6水平对子痫前期的诊断效能；
B上图：ELISA检测正常和子痫前期孕妇血清中PlGF水平(N为42vs.29)；下图：ROC曲线显示血清中PlGF水平对子痫前期的诊断效能；
C上图：ELISA检测正常和子痫前期孕妇血清中激活素A(C)水平(N为36vs.24)；下图：ROC 曲线显示血清中激活素A水平对子痫前期的诊断效能；
D，BMP6与PlGF血清浓度的Pearson相关性分析；
E，BMP6与激活素A血清浓度的Pearson相关性分析；
F，ROC曲线显示BMP6与PlGF、激活素A联合公式对子痫前期的诊断效能(N＝36vs.24)。联合公式＝BMP6×激活素A/PlGF；
G，联合公式与患者SBP的Pearson相关分析(N＝36vs.24)；
H，联合公式与患者血清肌酐水平的Pearson相关分析(N＝36vs.24)；
图2：A为HTR8/SVneo细胞分别用空白载体或BMP6(50ng/ml)处理24小时，分析细胞侵袭性；左图显示代表性图像，右图显示定量结果；比例尺，200μm；
B为HTR8/SVneo细胞分别用空白载体或BMP6(50ng/ml)处理24小时，分析内皮样管形成情况；左图显示代表性图像，右图显示定量结果；比例尺，200μm。
具体实施方式
应该指出，以下详细说明都是例示性的，旨在对本申请提供进一步的说明。除非另有指明，本申请使用的所有技术和科学术语具有与本申请所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本申请的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
下面结合具体的实施例对本发明作进一步的解释和说明。
实施例1
采集子痫前期孕妇和健康孕妇妊娠期间或分娩当天的清晨空腹血清样本，分装后于-80℃保存直至检测当天。
采用人BMP6 ELISA试剂盒(LSBio，#LS-F4538)对采集的子痫前期孕妇和健康孕妇的血清样本进行ELISA测定。具体根据ELISA试剂盒生产商的说明书进行检测。在美国Molecular Devices 公司的SpectraMax Plus酶标仪上，从450nm处读数减去540nm处读数，即可测得最终的吸光度值。
上述样品的血清BMP6水平可通过将吸光度值带入标准曲线的拟合公式(具体依据ELISA试剂盒生产商的说明书实施)计算得出。
结果表明，血清BMP6水平在子痫前期患者中相较正常孕妇显著升高(P<0.05)，如图1A-C 的上图所示。
通过ROC曲线进一步分析血清BMP6水平对所有子痫前期的诊断效果，结果显示血清BMP6 对子痫前期有较好的诊断效果(AUC：0.738)，如图1A-C的下图所示。且血清BMP6水平与现有诊断血清生物学标记物PlGF(图1D)、激活素A(图1E)有较好的相关性。
BMP6联合现有诊断血清生物学标记物PlGF、激活素A可提高现有诊断标记物对子痫前期诊断效果(AUC：0.943)，如图1F所示。BMP6联合PlGF、激活素A诊断与患者收缩压(SBP)(图 1G)和肌酐(图1H)水平正相关(P<0.05)。
实施例2
用人BMP6蛋白(50ng/ml)(R&D，#355-BM-010)或空白载体处理人滋养层细胞24小时。
将步骤1中处理后的细胞分别消化后在含0.1％(vol/vol)胎牛血清DMEM培养基中重悬，取250μl含 8x104个细胞的细胞悬液接种在处理好的Transwell小室中(Transwell小室已提前用40μl浓度为1 mg/ml的基质胶包被，Transwell小室为孔径为8μm，Transwell小室与基质胶均采购于BD Biosciences)。Transwell小室下层中加入750μl含10％(vol/vol)胎牛血清的DMEM培养基。将接种后的细胞在37℃孵育36h后，将膜上部未侵袭的细胞擦拭干净，将膜下部细胞用冷甲醇(-20℃) 固定并风干。细胞核用Hoechst 33258(Abcam，#ab228550)染色，Olympus IX73倒置显微镜成像， Image-J软件分析两组侵袭细胞数。
将10mg/mL的基质胶与含0.1％(vol/vol)胎牛血清DMEM培养基1：1(vol/vol)稀释，在96孔板的每孔中加入50μL稀释后的基质胶，37℃孵育2小时固化。将步骤1中处理后的细胞分别消化后于含空白载体或BMP6的0.1％胎牛血清DMEM培养液中重悬，然后将50μL含3×104个细胞的细胞悬液接种于已准备好的基质胶中，37℃孵育12小时。采用Olympus IX73倒置显微镜拍摄，观察小管形成，并采用ImageJ软件测量分析。
研究发现，BMP6(50ng/ml)处理24小时后相较对照组可显著增加人滋养层细胞的侵袭力和内皮特性获得(P<0.05)，从图2中可以看出，提示BMP6处理可能通过促进帮助滋养层细胞侵袭过程来改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，继而改善子痫前期的发展。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (7)
1.BMP6作为子痫前期早期诊断/预防/治疗标志物的应用。
2.BMP6联合PlGF和激活素A在子痫前期早期诊断中的应用。
3.一种子痫前期诊断试剂盒，其特征在于，所述诊断试剂盒中包括检测BMP6、PlGF和激活素A表达含量的试剂。
4.BMP6在制备子痫前期预防/治疗药物的应用。
5.如权利要求4所述的应用，其特征在于，预防/治疗药物的作用包括：
增加人滋养层细胞的侵袭力和内皮特性获得；
改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良，继而改善子痫前期的发展。
6.一种子痫前期预防/治疗方法，其特征在于，所述预防/治疗方法包括改善子痫前期早期的胎盘滋养细胞侵袭不足和血管重塑不良。
7.一种子痫前期的预防/治疗药物，其特征在于，所述药物以BMP6作为活性物质。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210073640.XA CN114470161B (zh) | 2022-01-21 | 2022-01-21 | 骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210073640.XA CN114470161B (zh) | 2022-01-21 | 2022-01-21 | 骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114470161A true CN114470161A (zh) | 2022-05-13 |
| CN114470161B CN114470161B (zh) | 2023-11-21 |
Family
ID=81471742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210073640.XA Active CN114470161B (zh) | 2022-01-21 | 2022-01-21 | 骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114470161B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115873943A (zh) * | 2023-02-13 | 2023-03-31 | 山东大学 | 骨形态发生蛋白2在子痫前期诊断、预防和治疗中的应用 |
-
2022
- 2022-01-21 CN CN202210073640.XA patent/CN114470161B/zh active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115873943A (zh) * | 2023-02-13 | 2023-03-31 | 山东大学 | 骨形态发生蛋白2在子痫前期诊断、预防和治疗中的应用 |
| CN115873943B (zh) * | 2023-02-13 | 2024-03-29 | 山东大学 | 骨形态发生蛋白2在子痫前期诊断、预防和治疗中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114470161B (zh) | 2023-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Garovic et al. | Urinary podocyte excretion as a marker for preeclampsia | |
| Baumann et al. | First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia | |
| US20100137263A1 (en) | Assay for the detection of biomarkers associated with pregnancy related conditions | |
| Kanter et al. | Angiogenic dysfunction in molar pregnancy | |
| Klentzrics et al. | Placental protein 14 in cycles with normal and retarded endometrial differentiation | |
| US20140030743A1 (en) | Markers for preeclampsia | |
| Fritz et al. | Noninvasive detection of trophoblast protein signatures linked to early pregnancy loss using trophoblast retrieval and isolation from the cervix (TRIC) | |
| Kurtoglu et al. | Role of vascular endothelial growth factor and placental growth factor expression on placenta structure in pre‐eclamptic pregnancy | |
| RU2693412C1 (ru) | Способ прогнозирования ранней и поздней преэклампсии | |
| CN114470161A (zh) | 骨形态发生蛋白6在子痫前期早期诊断、预防及治疗中的应用 | |
| US20080131867A1 (en) | Method for Determining the Effectiveness of a Treatment for Preeclampsia | |
| van Wezenbeek et al. | Interplay of sex hormones and long-term right ventricular adaptation in a Dutch PAH-cohort | |
| Merviel et al. | Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years | |
| Parker et al. | Fetal fibronectin in the cervicovaginal fluid of women with threatened preterm labour as a predictor of delivery before 34 weeks' gestation | |
| JP4625800B2 (ja) | マリノブファゲニンの増加を利用して子癇前症の有無を判定する方法及び関連装置 | |
| Avendanha et al. | Potential urinary biomarkers in preeclampsia: a narrative review | |
| Mello et al. | Prediction of the development of pregnancy-induced hypertensive disorders in high-risk pregnant women by artificial neural networks | |
| CN112180098B (zh) | 胎盘相关疾病标志物的筛选方法及标志物 | |
| EP2726631A1 (en) | Method for diagnosing preeclampsia | |
| Mackillop et al. | CKD Patterns and of Pregnancy | |
| US7674590B2 (en) | Methods for diagnosing and for monitoring the treatment of recurrent spontaneous abortion | |
| RU2782110C1 (ru) | Способ прогнозирования невынашивания беременности в ранние сроки путем определения сосудистого эндотелиального фактора роста и гипоксией индуцируемого фактора 1α в сыворотке крови беременных с цитомегаловирусной инфекцией | |
| EP3502704B1 (en) | Method, apparatus and computer program for predicting severity and prognosis of cardiovascular disease using vegf-a value in blood of a subject | |
| Bayram et al. | The Study the correlation between Human Chorionic Gonadotropin Hormone and Some Biochemical Parameters in Iraqi Women with Pregnancy-Induced Hypertension | |
| Ponomareva et al. | Investigation of Blood Biochemical Parameters as Predictors of the Severity of Early Toxicosis in Pregnant Women |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |