CN109212228A - Mif作为早期帕金森病诊断的生物标志物在制备帕金森病诊断试剂中的用途 - Google Patents
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Abstract
本发明公开了巨噬细胞迁移抑制因子(MIF)作为早期帕金森病诊断的生物标志物在制备帕金森病诊断试剂中的用途。采用巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病适用于无创/微创样本采集方案；适合多种学历背景和身体状况的受检者；而且价格仅为50元左右，适合推广的检测方法。
Description
技术领域
本发明涉及一种用于诊断帕金森病的血液生物标志物，属于生物医药技术领域。
背景技术
帕金森病是一种严重威胁中老年人健康和生活质量的神经退行性疾病和运动障碍性疾病。帕金森病临床表现为运动迟缓、肌紧张和静止性震颤，以及进行性认知功能减退。迄今为止，临床尚无可治愈帕金森病的手段，且其发病率逐年增加，因而早诊断早干预是目前学界的共识。临床也迫切需要无创或微创，灵敏特异，成本低的早期诊断方法。
临床病理分析结果提示早在帕金森病临床症状出现20年前，患者脑部就开始出现小胶质细胞激活和多巴胺能神经元丢失。
发明内容
本发明要解决的技术问题是克服帕金森病早期很难诊断的缺陷，提供一种用于诊断帕金森病的血液生物标志物。
为了解决上述技术问题，本发明提供了如下的技术方案：
巨噬细胞迁移抑制因子(MIF)作为早期帕金森病诊断的生物标志物在制备帕金森病诊断试剂中的用途。
一种通过检测巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病的方法，包括以下步骤：
1)、获取组织样本，检测巨噬细胞迁移抑制因子水平；
2)、将所检测到的巨噬细胞迁移抑制因子(MIF)的水平与正常水平进行比较。
优选的，组织样本为血浆或血清样本。
一种通过检测巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病的试剂盒，其包括：MIF标准品、封闭液、稀释液、生物素标记的检测MIF抗体、HRP标记的链霉亲和素、包被有MIF检测抗体的酶标板、底物显色液A和底物显色液B。
本发明所达到的有益效果是：采用巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病适用于无创/微创样本采集方案；适合多种学历背景和身体状况的受检者；而且价格仅为50元左右，适合推广的检测方法。
附图说明
附图用来提供对本发明的进一步理解，并且构成说明书的一部分，与本发明的实施例一起用于解释本发明，并不构成对本发明的限制。在附图中：
图1是本发明实施例中模型组小鼠脑组织纹状体中的巨噬细胞迁移抑制因子(MIF)的蛋白质免疫印迹结果；
图2是PD病人血清中的巨噬细胞迁移抑制因子(MIF)的酶联免疫吸附试验结果。
具体实施方式
以下结合附图对本发明的优选实施例进行说明，应当理解，此处所描述的优选实施例仅用于说明和解释本发明，并不用于限定本发明。
实施例
本方案采用国际通用的慢性帕金森病模型，步骤为：①8周龄雄性C57BL小鼠40只，随机分为两组，每组20只，一组注射生理盐水，一组注射1-甲基-4-苯基-1,2,4,5-四氢吡啶(MPTP)，25mg/kg剂量注射，每周注射2次，连续注射5周；本方案在注射第四周时，即小鼠为12周龄时处死小鼠，取样，通过蛋白质免疫印迹方法检测纹状体区MIF的表达量。
蛋白质免疫印迹步骤：
①组织/细胞蛋白提取
首先配制细胞裂解液，细胞裂解液配方为：50mM HEPES(pH 7.4)，1％NP-40，0.05％SDS，150mM NaCl，100mM NaF，1mM EGTA，4℃保存。使用前再加入蛋白酶抑制剂cocktail和磷酸酶抑制剂phosSTOP。细胞收集后先用预冷PBS洗一遍除去血清和培养基成分(组织则在取材时需用生理盐水灌流)，然后加入适当体积细胞裂解液，4℃旋转孵育20min(组织需要用组织匀浆器先匀浆后再孵育，5000rpm，15s)。最后4℃，12000×g离心15min，取上清，进行蛋白浓度测定。根据蛋白浓度测定结果，取相同量总蛋白，加入细胞裂解液调平，并加入适当体积6×上样缓冲液，95℃加热10min。
②蛋白浓度测定
本研究蛋白浓度测定均采用BCA法，主要步骤如下：1.按照50倍体积试剂A与1倍体积试剂B混合，加入到96孔板中，每一孔100μl；2.根据设定好的标准曲线值加入相应体积预先稀释好的BSA标准品，做浓度梯度-吸光度曲线；3.同时各孔相应加入1μl细胞(组织)裂解液离心上清(或者将上清用去离子水先进行适当稀释)；4.37℃孵育30min，再用多功能酶标仪读取462nm波长处吸光值；5.根据标准品的吸光值计算标准曲线；6.根据标准曲线计算细胞(组织)裂解液离心上清总蛋白浓度；7.将所有细胞/组织裂解液稀释到同样浓度，并尽量控制总蛋白浓度在2～10μg/μl之间。
③蛋白质免疫印迹(western blot)
主要步骤如下：①配制分离胶浓度为15％的聚丙烯酰氨凝胶进行SDS-PAGE电泳；②湿转法转膜，250mA恒流转膜90min；③5％脱脂乳/TBST室温封闭1h；④按照1:1000将MIF和GAPDH抗体分别用含0.1％叠氮钠的2％BSA/TBS稀释，之后与膜4℃孵育过夜；⑤TBST洗膜3次，每次5min；⑥将膜与对应种属的适当HRP标记二抗孵育(MIF抗体种属为兔，GAPDH抗体种属为小鼠)；⑦化学发光法结合X光片显影技术成像；⑧扫描仪扫描显影结果。
附图1的蛋白质免疫印迹结果显示注射MPTP4周时，模型组小鼠脑组织纹状体中的巨噬细胞迁移抑制因子(MIF)表达量显著升高。
收集帕金森病人及同龄对照人群血清，用人巨噬细胞迁移抑制因子(MIF)的ELISA检测试剂盒检测血清中MIF的含量。根据试剂盒(Human MIF Quantikine ELISA Kit，R&Dsystems)说明书，操作步骤为：①用300μl稀释液封闭酶标板，室温孵育1h；②用200μl PBS缓冲液将酶标板洗3遍，2min/遍，用酶标板旋转混匀仪旋转清洗，然后将液体倒去并在干净的纸塔将液体拍干；③将100μl稀释好的标准品或样品加入到酶标板中，室温孵育3h；④重复步骤②；⑤加入100μl稀释好的检测抗体，室温孵育2h；⑥重复步骤②；⑦加入100μl稀释好的HRP标记的链霉亲和素，室温孵育20min；⑧重复步骤②；⑨加入100μl底物显色液A/B混合物，室温避光孵育15-20min；⑩加入100μl终止液(2M硫酸)，酶标仪检测OD450和OD570吸光值，根据标准品OD值和对应浓度计算标准曲线，再根据标准曲线计算样本中MIF的含量。
酶联免疫吸附试验结果显示PD病人血清中的巨噬细胞迁移抑制因子(MIF)的含量显著高于健康人群(健康人群与PD病人年龄无显著差异)，表明巨噬细胞迁移抑制因子可作为诊断PD的诊断标志物，附图2的结果表明，PD阳性阈值可设置为2300pg/ml。根据该阈值，能够对50％的PD病人进行确诊。
最后应说明的是：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，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。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 (4)
1.巨噬细胞迁移抑制因子(MIF)作为早期帕金森病诊断的生物标志物在制备帕金森病诊断试剂中的用途。
2.一种通过检测巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病的方法，其特征在于，包括以下步骤：
1)、获取组织样本，检测巨噬细胞迁移抑制因子水平；
2)、将所检测到的巨噬细胞迁移抑制因子(MIF)的水平与正常水平进行比较。
3.如权利要求2所述的方法，其特征在于，所述的组织样本为血浆或血清样本。
4.一种通过检测巨噬细胞迁移抑制因子(MIF)诊断早期帕金森病的试剂盒，其包括：MIF标准品、封闭液、稀释液、生物素标记的检测MIF抗体、HRP标记的链霉亲和素、包被有MIF检测抗体的酶标板、底物显色液A和底物显色液B。
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030099653A1 (en) * | 1993-05-17 | 2003-05-29 | Bucala Richard J. | Inhibition of migration inhibitory factor in the treatment of diseases involving cytokine-mediated toxicity |
| CA2751161A1 (en) * | 2008-12-30 | 2010-07-08 | Children's Medical Center Corporation | Method of predicting acute appendicitis |
| CA2391392C (en) * | 1999-11-26 | 2012-07-17 | Herwig Brunner | Methods for screening candidate drugs that disrupt mif and jab1 interaction, mif and jab1 complex, antibodies and uses thereof |
| CN103988076A (zh) * | 2011-08-12 | 2014-08-13 | 阿尔弗雷德医疗集团 | 包括测量巨噬细胞移动抑制因子（mif）的血浆浓度的诊断、预后或治疗急性冠状动脉综合征（acs）的方法 |
| US20150253342A1 (en) * | 2009-04-03 | 2015-09-10 | Biomerieux | Prodefensin-a6 assay method for the in vitro diagnosis of colorectal cancer |
| CN105277715A (zh) * | 2015-05-28 | 2016-01-27 | 广州凯拓生物科技开发有限公司 | 巨噬细胞迁移抑制因子(mif)作为早期阿尔茨海默病血清分子标志物 |
| WO2018119001A1 (en) * | 2016-12-19 | 2018-06-28 | Fred Hutchinson Cancer Research Center | Peptide-antibody compositions and methods of use thereof |
-
2018
- 2018-09-10 CN CN201811047997.0A patent/CN109212228A/zh active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030099653A1 (en) * | 1993-05-17 | 2003-05-29 | Bucala Richard J. | Inhibition of migration inhibitory factor in the treatment of diseases involving cytokine-mediated toxicity |
| CA2391392C (en) * | 1999-11-26 | 2012-07-17 | Herwig Brunner | Methods for screening candidate drugs that disrupt mif and jab1 interaction, mif and jab1 complex, antibodies and uses thereof |
| CA2751161A1 (en) * | 2008-12-30 | 2010-07-08 | Children's Medical Center Corporation | Method of predicting acute appendicitis |
| US20150253342A1 (en) * | 2009-04-03 | 2015-09-10 | Biomerieux | Prodefensin-a6 assay method for the in vitro diagnosis of colorectal cancer |
| CN103988076A (zh) * | 2011-08-12 | 2014-08-13 | 阿尔弗雷德医疗集团 | 包括测量巨噬细胞移动抑制因子（mif）的血浆浓度的诊断、预后或治疗急性冠状动脉综合征（acs）的方法 |
| CN105277715A (zh) * | 2015-05-28 | 2016-01-27 | 广州凯拓生物科技开发有限公司 | 巨噬细胞迁移抑制因子(mif)作为早期阿尔茨海默病血清分子标志物 |
| WO2018119001A1 (en) * | 2016-12-19 | 2018-06-28 | Fred Hutchinson Cancer Research Center | Peptide-antibody compositions and methods of use thereof |
Non-Patent Citations (4)
| Title |
|---|
| "Science:研究鉴定出导致脑细胞死亡的罪魁祸首 ", 《现代生物医学进展》 * |
| ALESSANDRA NICOLETTI ET AL.: "Parkinson’s disease is associated with increased serum levels of macrophage migration inhibitory factor", 《CYTOKINE》 * |
| R&D SYSTEMS INC: "《Instruction manual of DMF00B》", 15 March 2016 * |
| 刘晓蕾: "成人斯蒂尔病发病机制及其相关临床研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110964801A (zh) * | 2019-11-06 | 2020-04-07 | 华南理工大学 | hsa-miRNA-451a在制备诊断帕金森病认知功能障碍分子标志物中的应用 |
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