WO2022170651A1 - 以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用 - Google Patents

以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用 Download PDF

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WO2022170651A1
WO2022170651A1 PCT/CN2021/078832 CN2021078832W WO2022170651A1 WO 2022170651 A1 WO2022170651 A1 WO 2022170651A1 CN 2021078832 W CN2021078832 W CN 2021078832W WO 2022170651 A1 WO2022170651 A1 WO 2022170651A1
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lipomycin
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hypertension
detection
detection tool
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PCT/CN2021/078832
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马鑫
周婷婷
王志玮
刘靓靓
肖望
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江南大学
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography

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  • the invention relates to the technical field of biomarkers, in particular to an application of using alpha-lipomycin as a marker for detecting and diagnosing hypertension to prepare a corresponding detection tool.
  • Cardiovascular disease remains the leading cause of human health and death. There is a close causal relationship between the level of blood pressure and the risk of cardiovascular and cerebrovascular disease and death. At present, the number of cardiovascular disease patients in China has exceeded 290 million, of which 245 million are hypertensive. Although elevated blood pressure is the most important clinical manifestation of hypertension, it is not necessarily the only and ideal diagnostic criterion. In the occurrence and development of hypertension, there are often a variety of metabolic disorders, such as obesity, impaired glucose tolerance, dyslipidemia and other metabolic disorders, which are common in hypertensive patients to different degrees and in different combinations. Therefore, blood lipids, blood sugar, and harmful substances produced by the body's metabolism may be used as predictors of hypertension.
  • serum levels of TNF- ⁇ and IL-6 can be used to clinically predict the onset and prognosis of gestational hypertension (Serum levels of TNF- ⁇ and IL-6 are associated with pregnancy-induced hypertension. Reproductive Science, 2016; 23( 10):1402-1408).
  • the serum fibrinogen (Fib) content in elderly patients with essential hypertension is significantly increased, and it is related to the plaque area of the blood vessel (Effect of plasma fibrinogen, high-sensitive C-reactive protein, and cigarette smoking on carotid atherosclerosis: the Suita Study. J Stroke Cerebrovasc Dis, 2015;24(10):2385-2389). Therefore, Fib is a sensitive indicator for predicting subclinical atherosclerosis and may be an independent predictor of coronary atherosclerotic disease severity.
  • the applicant of the present invention provides an application of preparing a corresponding detection tool by using ⁇ -lipomycin as a marker for detecting and diagnosing hypertension.
  • the ⁇ -lipomycin of the invention has relatively high content in the hypertensive model mice and hypertensive patients, and can be used for establishing detection methods or preparing detection and diagnosis kits for auxiliary diagnosis of hypertension and prehypertension.
  • ⁇ -lipomycin can increase blood pressure in mice through TRPV4, indicating that the higher the content of ⁇ -lipomycin in the body, the greater the risk of hypertension. It can be used to establish detection methods or prepare diagnostic kits for auxiliary assessment of hypertension and prehypertension risk prediction.
  • the detection object of the detection tool is a sample to be tested collected from a subject.
  • the detection limit of the detection tool for ⁇ -lipomycin is 0.01 ng/ml.
  • the sample to be tested collected from the subject is whole blood, plasma or serum; when the concentration of ⁇ -lipomycin in the sample to be tested collected from the subject is above a specified threshold, it means that the subject has Likelihood of hypertensive disease.
  • the subject is human or murine.
  • step (2) the level value obtained in step (1) is compared with the reference value
  • the method for determining the level of the marker in the test sample of the subject is a mass spectrometry detection method; before step (1), it also includes the step of processing the sample to be tested, and the processing method is to treat the non-anticoagulated blood of the subject by 5 mL , stand in the dark for 2h at room temperature, centrifuge at 3000rpm for 10min, and separate the serum.
  • the reference value is the concentration of ⁇ -lipomycin in healthy people, which is 0-0.5ng/ml.
  • the hypertension is a hypertensive disease in which the systolic blood pressure of the human body is detected to be ⁇ 140 mmHg and the diastolic blood pressure is ⁇ 90 mmHg.
  • a detection tool for hypertension is a self-diagnostic reagent, chip, carrier or kit.
  • a method of collecting data for assisting in the determination of hypertension, the determination of alpha-lipomycin in blood collected from a subject who is not clear about whether he has hypertension or a subject whose stage of hypertension is uncertain concentration was measured.
  • a method for detecting the marker for non-diagnostic purposes comprising the steps of:
  • step (2) Add the serum collected in step (1) into pre-cooled anhydrous methanol (containing 0.1% BHT) at a ratio of 1:3, fully vortex evenly, and centrifuge at 4°C for 10 min at 14000g; collect all the supernatants;
  • step (3) Blow dry the liquid obtained in step (2) with nitrogen gas in the sample nitrogen blowing concentrator, and set the temperature to 20°C. After drying, the sample is reconstituted with 300 ⁇ L of anhydrous methanol, mixed evenly at 4°C, and centrifuged at 14000g. 5min, take 200 ⁇ L of supernatant on the machine for testing;
  • the samples separated by UPLC entered the mass spectrometer for identification and quantitative analysis.
  • the mass spectrometry detection conditions were as follows: the multistage reaction monitoring mode (MRM) was used for detection in ESI+ mode, the ion source temperature was 100 °C, and the capillary voltage and cone voltage were set as 3.5kv, 20V.
  • the molecular weight of the primary mass spectrometer was 588, and the characteristic fragments produced by the secondary mass spectrometry were 358, 424 and 458.
  • the present invention finds for the first time that there is a relationship between ⁇ -lipomycin and salt-induced hypertension, and the content of ⁇ -lipomycin in salt-induced hypertension model mice and hypertensive patients is relatively high. And ⁇ -lipomycin can increase blood pressure in mice through TRPV4, indicating that the higher the content of ⁇ -lipomycin in the body, the greater the risk of hypertension. It can be used to establish detection methods or prepare diagnostic kits for auxiliary assessment of hypertension and prehypertension risk prediction.
  • Figure 1 shows the level of ⁇ -lipomycin in hypertensive mice induced by high-salt diet
  • Figure 2 shows the level of ⁇ -lipomycin in the hypertensive population
  • Figure 3 is a graph showing the relationship between ⁇ -lipomycin content and salt intake in hypertensive people.
  • Figure 4 is a graph showing the relationship between ⁇ -lipomycin and blood pressure elevation in normal mice.
  • Fig. 5 is a graph showing the relationship between ⁇ -lipomycin increasing blood pressure and TRPV4 in normal mice.
  • Non-invasive blood pressure testing equipment American IITC
  • Nitrogen blowing concentrator Chengdu Yayuan Technology Co., Ltd.
  • Orbital blood was collected from the hypertensive mice in the experimental group and the mice in the blank group with 500 ⁇ L of non-anticoagulated blood, left standing in the dark for 2 h at room temperature, centrifuged at 3000 rpm for 10 min, and the separated serum was collected; the collected serum was in a ratio of 1:3 Pre-cooled anhydrous methanol (containing 0.1% BHT) was added, fully vortexed, and then centrifuged at 14000g for 10 min at 4°C. All supernatants were collected; the resulting liquid was blown dry with nitrogen in a sample nitrogen blowing concentrator, and the temperature was set to 20°C.
  • Pre-cooled anhydrous methanol containing 0.1% BHT
  • the sample was reconstituted with 200 ⁇ L of anhydrous methanol, and after mixing evenly, centrifuged at 14,000 g for 5 min at 4°C, and took 170 ⁇ L of the supernatant to detect the content of ⁇ -lipomycin by UPLC-MS; during the detection process, the flow rate was set to 0.3 ml /min, the column temperature was fixed at 45 °C, and the injection volume was set to 5 ⁇ L.
  • Mobile phase A was acetonitrile and mobile phase B was 0.1% formic acid.
  • the samples separated by UPLC enter the mass spectrometer for identification and quantitative analysis.
  • the detection conditions of mass spectrometry are as follows: the multistage reaction monitoring mode (MRM) is used for detection in ESI+ mode, the ion source temperature is 100 °C, the capillary voltage and cone voltage are set to 3.5 kV and 20 V, respectively, the molecular weight of the primary mass spectrometer is 588, and the secondary mass spectrometer is set to 588.
  • MRM multistage reaction monitoring mode
  • the ion source temperature is 100 °C
  • the capillary voltage and cone voltage are set to 3.5 kV and 20 V, respectively
  • the molecular weight of the primary mass spectrometer is 588
  • the secondary mass spectrometer is set to 588.
  • the resulting feature fragments are 358, 424 and 458.
  • Inclusion criteria healthy people or clinically diagnosed hypertension.
  • Exclusion criteria (1) Known or suspected secondary hypertension; (2) Severe chronic diseases (including heart failure, renal failure, lung disease, rheumatism, stroke, gastrointestinal disease or blood disease, etc.) ; (3) Received antibiotics or probiotics in the past 1 month; (4) Severe cardiovascular and cerebrovascular diseases and related surgical history; (5) Gastrointestinal inflammation or taking prescription anti-inflammatory drugs or may affect Supplements/drugs for inflammation; (6) Experienced cholecystectomy, intestinal resection or gastrectomy; (7) Malignant tumors; (8) Pregnant women; (9) Those who are allergic to drugs; enrollee.
  • the blood samples of hypertensive people in the hypertensive group and healthy people in the non-hypertensive group were collected to detect the content of ⁇ -lipomycin in serum.
  • Each person collected 5 mL of non-anticoagulated blood, left it for 2 h at room temperature in the dark, centrifuged at 3000 rpm for 10 min, collected the separated serum, and detected the content of ⁇ -lipomycin.
  • the processing method of serum samples and the detection conditions of UPLC-MS are the same as those in Example 1.
  • Serum ⁇ -lipomycin content is correlated with salt intake in hypertensive population.
  • the 24-hour urinary sodium value is clinically used as the "gold indicator” to reflect the daily sodium chloride intake of patients.
  • We collected 24-hour urine samples from hypertensive patients (n 56) with a regular diet, and measured the concentration of urinary sodium by ion electrode method; Pearson correlation analysis.
  • Tail vein injection of ⁇ -lipomycin induces an acute increase in blood pressure in normal mice.
  • mice 10 healthy male C57BL/6J mice of 18-20 g were taken and randomly divided into two groups, one of which was the solvent control group and the other was the ⁇ -lipomycin group.

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Abstract

以α-脂霉素作为检测、诊断高血压的标志物来制备相应检测工具的应用。检测工具的检测对象为从受试者采集的待测样品。α-脂霉素在高血压模型鼠和高血压病人体内含量相对较高，可用于建立检测方法或制备检测、诊断试剂盒，用于高血压和高血压前期的辅助诊断和风险评估。

Description

以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用 技术领域
本发明涉及生物标志物技术领域，尤其是涉及一种以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用。
背景技术
心血管疾病仍然是危害人类健康和导致死亡的首要原因。血压的水平与心脑血管病发病和死亡风险之间存在密切的因果关系。目前中国心血管病患病人数已超过2.9亿，其中高血压高达2.45亿。血压水平增高虽然是高血压病的最重要临床表现，但不一定是唯一和理想的诊断标准。在高血压的发生发展过程中常合并有多种代谢紊乱，例如肥胖、糖耐量异常、血脂紊乱等代谢异常以不同程度、不同组合方式普遍存在于高血压患者群中。因此，血脂、血糖以及机体代谢产生的有害物质都可能作为高血压发生的预测因子。例如，血清中TNF-α和IL-6水平可用于临床预测妊娠期高血压的发病与预后(Serum levels of TNF-α and IL-6 are associated with pregnancy-induced hypertension.Reproductive Science,2016；23(10):1402-1408)。老年原发性高血压患者血清中纤维蛋白原(Fib)含量明显上升，并且与血管的斑块面积相关(Effect of plasma fibrinogen,high-sensitive C-reactive protein,and cigarette smoking on carotid atherosclerosis:the Suita Study.J Stroke Cerebrovasc Dis,2015；24(10):2385-2389)。因此，Fib是预测亚临床动脉粥样硬化的敏感指标，并可能成为冠状动脉粥样硬化疾病严重程度的独立预测因子。
经过调研，未见国内外学者对α-脂霉素与高血压相关性的相关文献报道(自PUBMED、CNKI、维普中国期刊网)，因此α-脂霉素在高血压生物标志物研究领域尚处于空白阶段。
发明内容
针对现有技术存在的上述问题，本发明申请人提供了一种以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用。本发明α-脂霉素在高血压模型鼠和高血压病人体内含量相对较高，可用于建立检测方法或制备检测、诊断试剂盒，用于高血压和高血压前期的辅助诊断。并且α-脂霉素可通过TRPV4 引起小鼠血压升高，说明体内α-脂霉的含量越高，患高血压的风险就越大。可用于建立检测方法或制备诊断试剂盒，用于高血压和高血压前期风险预测的辅助评估。
本发明的技术方案如下：
以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用，所述检测工具的检测对象为从受试者采集的待测样品。
所述检测工具对于α-脂霉素的检测限浓度为0.01ng/ml。
优选方案，从受试者采集的待测样品为全血、血浆或血清；在从受试者采集的待测样品中α-脂霉素的浓度为规定的阈值以上时，表示受试者具有患有高血压疾病的可能性。
所述受试者是人或鼠科动物。
当用于高血压诊断时，其包括以下步骤：
(1)测定受试者待测样品中α-脂霉素的水平值；
(2)将步骤(1)得到的水平值与参照值进行比较；
(3)当待测样品中α-脂霉素的浓度高于参照值时，受试者具有患有高血压疾病的可能性。
优选方案，确定标志物在受试者待测样品中的水平的方法为质谱检测方法；步骤(1)前还包括处理待测样品的步骤，处理方法为将受试者的非抗凝血5mL，室温下避光静置2h，3000rpm离心10min，分离出血清。
步骤(2)中，所述参照值为健康人群的α-脂霉素浓度，为0-0.5ng/ml。
所述高血压是检测到人体的收缩压≥140毫米汞柱，舒张压在≥90毫米汞柱的高血压疾病。
一种高血压的检测工具，所述检测工具为自诊断试剂、芯片、载体或试剂盒。
一种收集用于辅助高血压判定的数据的方法，对从不清楚是否患有高血压的受试者或者高血压的病期不确定的受试者采集的血液中的α-脂霉素的浓度进行测定。
一种非诊断目的的所述标志物的检测方法，所述方法包括以下步骤：
(1)取受试者的非抗凝血5mL，室温下避光静置2h，3000rpm离心10min，收集分离出的血清；
(2)将步骤(1)收集到的血清按1:3的比例加入预冷的无水甲醇(含0.1％BHT)，充分涡旋均匀后4℃，14000g离心10min；收集全部上清；
(3)将步骤(2)得到的液体在样品氮吹浓缩仪中用氮气吹干，温度设定为20℃，吹干后样品使用300μL无水甲醇复溶，混合均匀后4℃，14000g离心5min，取200μL上清上机进行测试；
(4)质谱检仪上测试，流速均设定为0.3ml/min，柱温固定在45℃，进样量设定为5μL；流动相A为乙腈，流动相B为0.1％甲酸。
经UPLC分离后的样本进入质谱仪进行鉴定和定量分析，质谱检测条件如下：采用多级反应监测模式(MRM)在ESI+模式下检测，离子源温度100℃，毛细管电压和锥孔电压分别设置为3.5kv、20V。一级质谱分子量为588，二级质谱产生的特征碎片为358，424和458。
本发明有益的技术效果在于：
本发明首次发现α-脂霉素与盐诱导的高血压之间存在联系，α-脂霉素在盐诱导的高血压模型鼠和高血压病人体内含量相对较高。并且α-脂霉素可通过TRPV4引起小鼠血压升高，说明体内α-脂霉的含量越高，患高血压的风险就越大。可用于建立检测方法或制备诊断试剂盒，用于高血压和高血压前期风险预测的辅助评估。
附图说明
图1为高盐饮食诱导的高血压小鼠体内α-脂霉素的水平值；
图2为高血压人群体内α-脂霉素的水平值；
图3为高血压人群体内α-脂霉素含量与盐摄取量的关系图。
图4为α-脂霉素与正常小鼠血压升高的关系图。
图5为α-脂霉素升高正常小鼠的血压与TRPV4的关系图。
具体实施方式
下面结合附图和实施例，对本发明进行具体描述。
具体实施方式所涉及的动物、实验仪器与试剂来源：
C57BL/6J小鼠：上海斯莱克实验动物有限责任公司
无创血压测试设备：美国IITC
超高效液相色谱串联四极杆飞行时间质谱联用仪(UPLC-MS)：美国Waters
氮吹浓缩仪：成都雅源科技有限公司
离心机：Thermo Fisher
高盐饲料：南通特洛菲饲料科技有限公司
甲醇：国药集团
2,6-二叔丁基对甲酚(BHT)：阿拉丁
实施例1：
高盐饮食诱导的高血压小鼠体内α-脂霉素的水平测定。
取18-20g健康的雄性C57BL/6J小鼠共13只，分成两组，分别为实验组(n＝7)和空白组(n＝6)；其中实验组使用8％高盐饲料饲喂，空白组正常饮食，喂养五周后，利用尾套法测量小鼠血压，实验组得到高盐饮食诱导的高血压小鼠。
眼眶采血分别收集实验组高血压小鼠和空白组小鼠非抗凝血500μL，室温下避光静置2h，3000rpm离心10min，收集分离出的血清；将收集到的血清按1:3的比例加入预冷的无水甲醇(含0.1％BHT)，充分涡旋均匀后4℃，14000g离心10min。收集全部上清；将得到的液体在样品氮吹浓缩仪中用氮气吹干，温度设定为20℃。吹干后样品使用200μL无水甲醇复溶，混合均匀后4℃，14000g离心5min，取170μL上清利用UPLC-MS检测α-脂霉素的含量；检测过程中，流速均设定为0.3ml/min，柱温固定在45℃，进样量设定为5μL。流动相A为乙腈，流动相B为0.1％甲酸。经UPLC分离后的样本进入质谱仪进行鉴定和定量分析。质谱检测条件如下：采用多级反应监测模式(MRM)在ESI+模式下检测，离子源温度100℃，毛细管电压和锥孔电压分别设置为3.5kv和20V，一级质谱分子量为588，二级质谱产生的特征碎片为358，424和458。
小鼠体内α-脂霉素的水平测定结果如图1所示，由图1可以看出，空白组中正常饮食的小鼠血清中α-脂霉素的含量约为0.01586±0.002369ng/ml，实验组中高盐饮食的高血压小鼠血清中含量约为0.2624±0.01663ng/ml。因此，高血压小鼠血清中α-脂霉素的含量是要明显高于正常血压小鼠血清中α-脂霉素的含量，并且差异有显著性(P<0.001：***)。结果说明高盐饮食诱导的高血压小鼠体内α-脂霉素的水平较高。
实施例2：
高血压人群体内α-脂霉素的水平测定。
本次临床试验共招募到87名入组志愿者，使用电子血压计测量志愿者上臂血压。根据测量到的血压数值分成两组：非高血压组(n＝17)和高血压组(n＝70)。在安静状态下连续测量血压数值大于140/90毫米汞柱的志愿者，为高血压人群 被纳入高血压组，其余的健康人群归为非高血压组。所有志愿者均签署知情同意书，所有志愿者满足纳入和排除标准。标准如下：
纳入标准：健康人群或临床诊断为高血压。
排除标准：(1)已知或疑似为继发性高血压；(2)患有严重的慢性疾病(包括心力衰竭、肾功能衰竭、肺病、风湿、中风、胃肠道疾病或血液病等)；(3)在近1个月内接受过抗生素或益生菌治疗；(4)患有严重心脑血管疾病及相关手术史；(5)患有胃肠道炎症或者服用处方消炎药或可能影响炎症的补品/药物；(6)经历过胆囊切除，肠切除或胃切除手术；(7)恶性肿瘤；(8)妊娠期妇女；(9)药物使用过敏者；(10)研究者认为不适合入组者。
分别收集高血压组的高血压人群和非高血压组的健康人群的血液样本，对血清中α-脂霉素的含量进行检测。每个人采集非抗凝血5mL，室温下避光静置2h，3000rpm离心10min，收集分离出的血清，并进行α-脂霉素含量的检测。血清样本的处理方法和UPLC-MS的检测条件同实施例1。
测定结果如图2所示，由图2可以看出，健康人血清中α-脂霉素的含量约为0.18674±0.02983ng/ml，而高血压人群血清中含量约为1.20947±0.13151ng/ml，因此高血压人群组别血清中α-脂霉素的含量要明显高于健康人群组别，并且差异有显著性(P<0.01：**)。结果说明高血压人群体内α-脂霉素的水平较高。
实施例3：
高血压人群血清中α-脂霉素含量与盐摄取量相关。
由于临床上将24小时尿钠值作为反映患者每日氯化钠摄入量的“金指标”。我们收集了高血压患者(n＝56)常规膳食24小时尿样后，采用离子电极法测定尿钠浓度；并将高血压人群血清中α-脂霉素的含量与24小时尿钠值进行了皮尔森相关性分析。
结果如图3所示，高血压人群血清中α-脂霉素含量与病人每日盐摄取量(24小时尿钠)相关，差异有显著性(r＝0.623，P<0.001)。
实施例4：
α-脂霉素经尾静脉注射可诱导正常小鼠血压急性升高。
取18-20g健康的雄性C57BL/6J小鼠10只，随机分为2组，其中1组为溶 剂对照组，另一组为α-脂霉素组。分别尾静脉生理盐水或α-脂霉素(8mg/kg，n＝5)，采用尾套法实时监测小鼠血压波动。
结果如图4所示，化合物α-脂霉素作用于正常小鼠后，给药后30分钟至90分钟期间，其血压发生了明显升高，差异有显著性(P<0.001：***)。结果说明α-脂霉素能够升高正常小鼠的血压，引起高血压。
实施例5：
α-脂霉素经尾静脉注射不引起全身性TRPV4敲除小鼠血压急性升高。
取18-20g健康的雄性全身性TRPV4敲除小鼠10只，随机分为2组，其中1组为溶剂对照组，另一组为α-脂霉素组。分别尾静脉生理盐水或α-脂霉素(8mg/kg，n＝5)，采用尾套法实时监测小鼠血压波动。
结果如图5所示，化合物α-脂霉素作用于全身性TRPV4敲除小鼠后，小鼠的血压没发生明显变化，差异无显著性(ns)。结果说明α-脂霉素引起高血压依赖于TRPV4。

Claims (10)

  1. 以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用，其特征在于，所述检测工具的检测对象为从受试者采集的待测样品。
  2. 根据权利要求1所述的应用，其特征在于，所述检测工具对于α-脂霉素的检测限浓度为0.01ng/ml。
  3. 根据权利要求1所述的应用，其特征在于，从受试者采集的待测样品为全血、血浆或血清；在从受试者采集的待测样品中α-脂霉素的浓度为规定的阈值以上时，表示受试者具有患有高血压疾病的可能性。
  4. 根据权利要求1所述的应用，其特征在于，所述受试者是人或鼠科动物。
  5. 根据权利要求1所述的应用，其特征在于，当用于高血压诊断时，其包括以下步骤：
    (1)测定受试者待测样品中α-脂霉素的水平值；
    (2)将步骤(1)得到的水平值与参照值进行比较；
    (3)当待测样品中α-脂霉素的浓度高于参照值时，受试者具有患有高血压疾病的可能性。
  6. 根据权利要求5所述的应用，其特征在于，确定标志物在受试者待测样品中的水平的方法为质谱检测方法；步骤(1)前还包括处理待测样品的步骤，处理方法为将受试者的非抗凝血5mL，室温下避光静置2h，3000rpm离心10min，分离出血清。
  7. 根据权利要求5所述的应用，其特征在于，步骤(2)中，所述参照值为健康人群的α-脂霉素浓度，为0-0.5ng/ml。
  8. 根据权利要求1所述的应用，其特征在于，所述高血压是检测到人体的收缩压≥140毫米汞柱，舒张压在≥90毫米汞柱的高血压疾病。
  9. 一种权利要求1-8中任一应用制备得到的高血压的检测工具，其特征在于，所述检测工具为自诊断试剂、芯片、载体或试剂盒。
  10. 一种收集用于辅助高血压判定的数据的方法，其特征在于，对从不清楚是否患有高血压的受试者或者高血压的病期不确定的受试者采集的血液中的α-脂霉素的浓度进行测定。
PCT/CN2021/078832 2021-02-09 2021-03-03 以α-脂霉素作为检测、诊断高血压的标志物制备相应检测工具的应用 WO2022170651A1 (zh)

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