CN108152492A - 用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用 - Google Patents
用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用 Download PDFInfo
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- CN108152492A CN108152492A CN201711424114.9A CN201711424114A CN108152492A CN 108152492 A CN108152492 A CN 108152492A CN 201711424114 A CN201711424114 A CN 201711424114A CN 108152492 A CN108152492 A CN 108152492A
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Abstract
本发明涉及疾病检测领域,具体公开了一种用于检测缺血性脑卒中血脑屏障早期损伤的特异性抗体及其应用。所述抗体的特点在于,其仅特异性识别occludin蛋白的降解片段中的DHYETDYTTGGESC,而不识别occludin全长蛋白,因此,可用于特异性检测缺血性脑卒中的血脑屏障早期损伤,并可以排除血清中occludin全长蛋白对检测结果的影响,显著提高针对缺血性脑卒中血脑屏障早期损伤检测的特异性和准确率。
Description
技术领域
本发明涉及疾病检测领域,具体地说,涉及用于检测缺血性脑卒中血脑屏障早期损伤的特异性抗体及其应用。
背景技术
脑卒中以其高发病率和高致残率成为当前严重威胁人类健康的重要疾病,其中80%为缺血性脑卒中。最新发表在《柳叶刀》杂志的《全球疾病负担报告》表明,脑卒中已经成为中国第一位死亡原因。由于人口老龄化加速以及危险因素控制欠佳,我国脑卒中发病率正以每年8.7%的速度迅速攀升;仅北京地区每年卒中病人治疗费用就超过100亿,是沉重的社会和经济负担。
静脉溶栓是目前公认的治疗急性缺血性脑卒中最有效的方法之一。静脉溶栓可以最大限度地挽救缺血脑组织,改善神经功能,降低病人残疾程度,提高生存质量。组织纤溶酶原激活物(tissue-type plasminogen activator,tPA)是目前唯一通过FDA批准的用于治疗急性缺血性脑卒中的溶栓药物。但是,tPA溶栓有非常苛刻的时间窗限制,安全期为脑卒中发生3小时内,3-4.5小时为谨慎期。
由于时间窗苛刻,现阶段符合溶栓治疗适应症的病人比例很低。统计数字表明,发病后能够在时间窗内(3-4.5小时之内)到达医院、并且使用tPA溶栓的病人比例很低:发达国家不到5%,在我国仅有不到1.6%。
延迟溶栓的主要风险是脑出血并发症增加,导致病情加重甚至死亡。而脑血管破坏是出血转化发生的主要原因。早在脑缺血溶栓之前,脑血管就已经出现损伤,并随着缺血时间延长、血管损伤加重。溶栓治疗血流再通后,再灌注的血液从受损的血管中漏出,导致出血;加之tPA溶栓过程中血液纤溶***活性亢进,一旦发生出血很难及时止住,加重出血。
因此,亟需找到一种可以在发病早期评估血管损伤程度的标记物,用来筛选那些在溶栓时间窗外(超过4.5h)但血管条件良好、可以接受溶栓的病人,以及排除在3-4.5h溶栓时间窗内但有高出血转化风险的病人,从而使更多的脑卒中病人可以接受溶栓治疗。
目前,快速、准确地血液标记物检测早期血管损伤的方法,可以帮助评估早期出血转化风险,从而指导临床上脑卒中早期的tPA溶栓。而且,该方法还可以进一步预测脑组织保护药物的效能,因为绝大部分脑保护药物都不能直接通过血脑屏障。早期的血脑屏障损伤还可以用于评价脑损伤及判断预后,因此血脑屏障损伤的快速血液标记物检测还可以用于评价脑创伤的脑损伤程度。
研究发现,occludin降解片段可以作为评价血脑屏障损伤的血液标记物,从而确定血脑屏障损伤程度。但是目前还没有特异性识别occludin降解片段的方法,无法排除血清中occludin全长蛋白对检测结果的影响。而对血清中occludin全长蛋白的识别,会影响检测结果的准确性,造成误判。
因此,亟需提供一种可特异性识别occludin降解片段的物质或方法,提高检测的特异性和准确率。
发明内容
为了解决现有技术中存在的问题,本发明的目的是提供一种可以特异性识别血清中occludin降解片段的抗体及其应用,利用所述抗体对患者进行检测,可以排除血清中occludin全长蛋白对检测结果的影响,显著提高检测结果的特异性。通过检测样品中蛋白片段浓度,将可以用于判断缺血性脑卒中是否发生,以及发病程度。
为了实现本发明目的,本发明的技术方案如下:
第一方面,提供一种可以特异性识别血清中occludin降解片段的抗体,所述抗体可用于特异性检测缺血性脑卒中的血脑屏障早期损伤。
所述抗体的特点在于,其仅特异性识别occludin蛋白的降解片段中的DHYETDYTTGGESC,而不识别occludin全长蛋白。
进一步地,所述抗体的制备方法包括如下步骤:
(1)合成多肽DHYETDYTTGGESC;
(2)合成抗原:将步骤(1)合成的多肽与KLH偶联,得到KLH-多肽,作为免疫抗原;
偶联时,选择SuLfo-SMCC作为偶联剂;
(3)使用所述免疫抗原免疫动物,获得抗血清;
(4)使用抗原亲和柱,对所述抗血清进行抗体纯化,获得特异性抗体。
需要说明的是,上述多肽序列代表母本蛋白的序列,化学合成的多肽往往携带游离的氨基和游离的羧基,为了与母本蛋白更为接近,肽末端往往需要封闭,即N端乙酰化和C端酰胺化,这些修饰会减少多肽的总电荷,降低多肽的溶解度,也可以使肽模拟它在母本蛋白中α氨基和羧基的原始状态。
所述抗原亲和柱由步骤(1)合成的多肽连接到活化的SuLfolink Resin上制备得到。
所述动物可为家兔、小鼠、羊、马等,在本发明的一个具体实施方式中,选择新西兰白兔作为免疫动物,但在实际制备所述抗体的过程中,可使用的免疫动物并不局限于此。
在将新西兰白兔作为免疫动物的基础上,使用所述免疫抗原免疫动物,优选对其每14天加强免疫一次,共免疫4次,颈动脉取血,获得抗血清。
当选择其他动物作为免疫动物时,可根据具体情况,调整免疫间隔时间和免疫次数。
也可通过取心脏取血、静脉采血法,获得抗血清。
第二方面,本发明提供了所述抗体在制备检测缺血性脑卒中血脑屏障早期损伤试剂盒中的应用。
具体表现为,提供一种含有本发明所述抗体的试剂盒,所述试剂盒可用于检测缺血性脑卒中血脑屏障早期损伤。
其是通过借助本发明所述抗体能够特异性识别由缺血性脑卒中血脑屏障早期损伤所引起的occludin蛋白降解而产生的特异性降解片段,来检测缺血性脑卒中血脑屏障早期损伤是否发生。
作为优选,所述试剂盒为ELISA试剂盒,包括:包被有本发明所述抗体的固相载体,检测抗体、酶标抗体、标准抗原。
所述固相载体可为酶标板、聚苯乙烯或聚氯乙烯微量反应板及塑料管等。
进一步地,用于包被固相载体的所述抗体的使用浓度为0.1~1μg/mL。
更为具体地,本发明提供一种固相载体的制备方法:
(1)包被:用200mM NaHCO3缓冲液(pH9.6)稀释特异性抗体XW-OCLN-2,至终浓度为0.1~1μg/mL,向酶标板每孔加入100μL occludin特异性抗体稀释液,4℃冰箱过夜;
(2)冲洗:PBST冲洗酶标板各孔4次,每次5-10min;
(3)封闭:加封闭液1-10%BSA,37℃孵育1-2h;
(4)再冲洗:冲洗4次,晾干。
所述PBST 1000mL的制备方法为:Na2HPO4 2.72g;NaH2PO4 0.28g;NaCl9g;双蒸水1000mL;Tween20 500μL。
上述试剂或原料的用量进行等比例扩大或者缩小后的技术方案,与上述制备方法的实质相同,因此,所述固相载体的制备方法并不局限于上述具体用量条件。
例如,在上述制备方法中,可替换NaHCO3缓冲液为Na2CO3/NaHCO3缓冲液(pH9.6),加或不加叠氮钠等防腐剂。
封闭液可替换为不同浓度的明胶、Casein或山羊、马等动物血清。
所述检测抗体为经检测不予本特异性抗体结合,但可识别occludin蛋白的不同种属抗体(Thermo Fisher货号33-1500)。
所述酶标抗体为与检测抗体同种属的酶标二抗(中杉金桥ZB-2305)。
所述标准抗原为人工合成的可与本发明所述抗体相结合的小肽。
第三方面,本发明提供了所述抗体或试剂盒在检测缺血性脑卒中血脑屏障早期损伤中的应用。
具体为,利用本发明所述试剂盒对待检样本进行检测,依据检测结果(如光密度值)判断待检样本是否为发生血脑屏障早期损伤的急性缺血脑卒中病人。
本发明的有益效果在于:
本发明提供了仅特异性识别occludin蛋白的降解片段,而不识别occludin全长蛋白的特异性抗体,可以排除血清中occludin全长蛋白对检测结果的影响,显著提高针对缺血性脑卒中血脑屏障早期损伤检测的特异性和准确率。
附图说明
图1为本发明实施例1所述的人occludin蛋白序列的疏水性分析。
图2为本发明实施例1中血清中occludin水平的western blot检测图。
图3为本发明实施例3中急性缺血脑卒中病人和健康人血清中的occludin特异性降解片段的水平。
具体实施方式
下面将结合实施例对本发明的优选实施方式进行详细说明。需要理解的是以下实施例的给出仅是为了起到说明的目的,并不是用于对本发明的范围进行限制。本领域的技术人员在不背离本发明的宗旨和精神的情况下,可以对本发明进行各种修改和替换。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1特异性抗体的开发
本实施例用于说明本发明所述特异性抗体的开发过程,具体步骤如下:
1、根据人的occludin全长蛋白序列(AAB00195.1,如SEQ ID NO.1所示),经过疏水性分析(图1),判断该蛋白为多次跨膜蛋白,并预测适合进行抗原识别和抗体制备的多肽序列。从N-端至C-端,选取4段序列,进行多肽合成。
序列1#YRPDEFKPNHYAPSNC;
序列2#KTRRKMDRYDKSNIL;
序列3#DHYETDYTTGGESC;
序列4#SKLSHIKKMVGDYDR。
2、合成抗原:
分别将上述1#~4#多肽与KLH偶联(偶联剂为SuLfo-SMCC),得到KLH-多肽,作为1#~4#免疫抗原;
分别将上述1#~4#多肽与BSA偶联(偶联剂为戊二醛),得到BSA-多肽,作为1#~4#检测抗原。
3、用皮下注射多肽法,分别使用1#~4#免疫抗原免疫新西兰白兔。每14天加强免疫一次,共免疫4次。颈动脉取血,获得抗血清。
4、将步骤1合成的4种多肽连接到活化的SuLfolink Resin上,制备抗原亲和柱。
使用抗原亲和柱,对步骤3所得的抗血清进行抗体纯化,分别获得特异性抗体,对应的抗体编号为XW-OCLN-1,XW-OCLN-2,XW-OCLN-3,XW-OCLN-4。收集的洗脱液检测280nm处的吸光度,吸光度大于1.0的组分合并,对PBS透析。对透析后的抗体检测蛋白浓度,ELISA法测定抗体效价。
5、特异性抗体效价:采用BSA-多肽(1#~4#检测抗原)进行ELISA检测免疫反应效果(表1)。
表1 ELISA检测抗体效价
分别用浓度为1μg/mL的1#~4#检测抗原分别包被ELISA板,对应加入不同浓度的特异性抗体(XW-OCLN-1,XW-OCLN-2,XW-OCLN-3,XW-OCLN-4)和空白IgG。检测结果显示,纯化得到的特异性抗体可以特异识别检测抗原,效价很高,在浓度为1:80000时,仍可见明显特异性结合信号。
6、检测抗体对病人血清中occludin全长和片段的识别情况。
对同一个急性缺血脑卒中病人的血清,进行电泳、转膜,分别用XW-OCLN-1,XW-OCLN-2,XW-OCLN-3和XW-OCLN-4抗体孵育,western blot检测血清中occludin的水平,结果见图2。
由图2可以看到,XW-OCLN-1抗体可以识别occludin全长蛋白和20kDa的蛋白片段。
而XW-OCLN-2,XW-OCLN-3和XW-OCLN-4抗体则只识别蛋白片段,不识别occludin全长蛋白。
由此确定,XW-OCLN-2,XW-OCLN-3和XW-OCLN-4抗体可以特异性识别血清中occludin降解片段,可以排除血清中occludin全长蛋白对检测结果的影响,显著提高检测结果的特异性。
实施例2特异性检测缺血性脑卒中血脑屏障早期损伤的试剂盒
本实施例以实施例1步骤4获得的特异性抗体XW-OCLN-3为例,说明特异性检测缺血性脑卒中血脑屏障早期损伤的试剂盒,所述试剂盒为ELISA试剂盒,包括:包被有特异性抗体XW-OCLN-3的固相载体、检测抗体、酶标抗体、标准抗原。
其中:
所述固相载体的制备方法具体为:
(1)包被:用200mM NaHCO3缓冲液稀释特异性抗体XW-OCLN-3,至终浓度为1μg/mL,向酶标板每孔加入100μLoccludin特异性抗体稀释液,4℃冰箱过夜;
(2)冲洗:PBST冲洗酶标板各孔4次,每次5min;
(3)封闭:加封闭液10%BSA,37℃孵育2h;
(4)再冲洗:冲洗4次,室温晾干。
所述PBST1000mL的制备方法为:Na2HPO4 2.72g;NaH2PO40.28g;NaCl 9g;双蒸水1000mL;Tween 20 500μL。
所述检测抗体为经检测不予本特异性抗体结合,但可识别occludin蛋白的不同种属抗体(Thermo Fisher货号33-1500)。
所述酶标抗体为与检测抗体同种属的酶标二抗(中杉金桥ZB-2305)。
所述标准抗原为人工合成的可与本发明所述特异性抗体相结合的小肽。
实施例3检测试剂盒的应用
本实施例用于说明如何利用实施例2所制备的ELISA试剂盒,检测急性缺血脑卒中病人血清中occludin特异性降解片段的水平,从而衡量脑卒中病人血脑屏障早期损伤的情况。
本实施例利用实施例2所制备的ELISA试剂盒,针对6个急性缺血脑卒中病人和5个健康人的血清进行检测。
(1)采集急性缺血脑卒中病人和健康体检病人的血清;加入人血清100μL,37℃孵育2h,冲洗;
(2)加100μL检测抗体(Thermo Fisher货号33-1500),孵育2h,冲洗4次;
(3)加100μL二抗(中杉金桥ZB-2305),37℃温浴30min,冲洗;
(4)每孔加入TMB底物显色液90μL,37℃避光显色,30min后在酶标仪450nm波长,检测光密度值。根据已知不同浓度的标准品的光密度值,绘制标准曲线,根据标准曲线得出血清中occludin的片段的水平。
结果如图3所示,由图可知,急性缺血性脑卒中病人血清中occludin特异性降解片段的水平明显高于健康体检病人,表明本试剂盒可以识别血清中occludin的特异性降解片段。
应当理解的是,对上述实施例所用试剂或原料的用量进行等比例扩大或者缩小后的技术方案,与上述实施例的实质相同。
虽然,上文中已经用一般性说明及具体实施方案对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
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Claims (10)
1.一种用于特异性检测缺血性脑卒中血脑屏障早期损伤的抗体,其特征在于,所述抗体仅特异性识别occludin蛋白降解片段中的DHYETDYTTGGESC,而不识别occludin全长蛋白。
2.根据权利要求1所述的抗体,其特征在于,其制备方法包括如下步骤:
(1)合成多肽DHYETDYTTGGESC;
(2)合成抗原:将步骤(1)合成的多肽与KLH偶联,得到KLH-多肽,作为免疫抗原;
(3)使用所述免疫抗原免疫动物,获得抗血清;
(4)使用抗原亲和柱,对所述抗血清进行抗体纯化,获得特异性抗体。
3.根据权利要求2所述的抗体,其特征在于,所述动物为新西兰白兔。
4.根据权利要求2或3所述的抗体,其特征在于,使用所述免疫抗原免疫动物,每14天加强免疫一次,共免疫4次,颈动脉取血,获得抗血清。
5.含有权利要求1所述抗体的试剂盒。
6.根据权利要求5所述的试剂盒,其特征在于,所述试剂盒为ELISA试剂盒,包括:包被权利要求1~4任一项所述抗体的固相载体,检测抗体、酶标抗体、标准抗原。
7.根据权利要求6所述的试剂盒,其特征在于,包被固相载体的抗体的使用浓度为0.1~1μg/mL。
8.根据权利要求6所述的试剂盒,其特征在于,所述标准抗原为人工合成的可与权利要求1~4任一项所述抗体相结合的小肽。
9.权利要求1~4任一项所述的抗体在制备检测缺血性脑卒中血脑屏障早期损伤试剂盒中的应用。
10.根据权利要求9所述的应用,其特征在于,所述试剂盒为ELISA试剂盒,包括:包被权利要求1~4任一项所述抗体的固相载体,检测抗体、酶标抗体、标准抗原。
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KR101941308B1 (ko) * | 2011-01-28 | 2019-01-22 | 이뮤노사이언시스 랩. 인크. | 장, 혈액-뇌 장벽 투과성 검출 방법 및 테스트 물질 |
CN108152492B (zh) * | 2017-12-25 | 2019-03-08 | 首都医科大学宣武医院 | 用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用 |
-
2017
- 2017-12-25 CN CN201711424114.9A patent/CN108152492B/zh active Active
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2018
- 2018-12-17 WO PCT/CN2018/121503 patent/WO2019128758A1/zh active Application Filing
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2020
- 2020-06-23 US US16/910,058 patent/US20200385462A1/en not_active Abandoned
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2023
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140314737A1 (en) * | 2011-10-25 | 2014-10-23 | Stc.Unm | Blood Biomarker for Early Blood Brain Barrier Disruption in Ischemic Stroke |
CN105203749A (zh) * | 2015-09-22 | 2015-12-30 | 深圳市第二人民医院 | 一种可评估溶栓前脑出血风险的血清标记物及其应用 |
Non-Patent Citations (3)
Title |
---|
BERTHA C. ELIAS ET AL: "Phosphorylation of Tyr-398 and Tyr-402 in Occludin Prevents Its Interaction with ZO-1 and Destabilizes Its Assembly at the Tight Junctions.", J BIOL CHEM, vol. 284, no. 3, 16 January 2016 (2016-01-16), pages 1559 - 1569, XP055622442 * |
SHUHAI SHI等: "Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke.", 《STROKE》 * |
唐秋艳等主编: "《免疫诊断试剂实用技术》", 31 August 2009 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019128758A1 (zh) * | 2017-12-25 | 2019-07-04 | 首都医科大学宣武医院 | 用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用 |
CN110780078A (zh) * | 2019-11-12 | 2020-02-11 | 安徽恩禾生物技术有限公司 | 一种定量检测紧密连接相关蛋白Occludin的ELISA试剂盒 |
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US20200385462A1 (en) | 2020-12-10 |
WO2019128758A1 (zh) | 2019-07-04 |
US20230348591A1 (en) | 2023-11-02 |
CN108152492B (zh) | 2019-03-08 |
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