WO2020125530A1 - D-丝氨酸作为标志物在制备抑郁症诊断试剂盒中的应用及抑郁症诊断试剂盒 - Google Patents
D-丝氨酸作为标志物在制备抑郁症诊断试剂盒中的应用及抑郁症诊断试剂盒 Download PDFInfo
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- WO2020125530A1 WO2020125530A1 PCT/CN2019/124721 CN2019124721W WO2020125530A1 WO 2020125530 A1 WO2020125530 A1 WO 2020125530A1 CN 2019124721 W CN2019124721 W CN 2019124721W WO 2020125530 A1 WO2020125530 A1 WO 2020125530A1
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- 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
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/30—Psychoses; Psychiatry
- G01N2800/304—Mood disorders, e.g. bipolar, depression
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- the invention relates to the technical field of diagnosis of depression, in particular to the application of D-serine as a marker in the preparation of a diagnostic kit for depression and a diagnostic kit for depression.
- depression is a negative emotion. If the duration is too long, it will form a pathological mental illness, such as depression.
- Depression is a mental illness caused by a variety of reasons and the main symptom is persistent depression. Its clinical manifestations are diverse, often accompanied by anxiety, lack of pleasure and social disorders. Depression is a common disease in psychiatry, and the World Health Organization predicts that by 2020, depression will become the second most common disease.
- the first object of the present invention is to provide D-serine as a marker in the preparation of a diagnostic kit for depression, so as to alleviate the technical problems in the prior art.
- the second object of the present invention is to provide a diagnostic kit for depression, which detects whether or not depression is detected by detecting the content of D-serine, and provides a new strategy for the diagnosis of depression.
- the third object of the present invention is to provide the use of D-serine in the preparation of a medicament for treating depression.
- the invention provides the application of D-serine as a marker in the preparation of a diagnostic kit for depression.
- the detection sample of the depression diagnosis kit is cerebrospinal fluid.
- the depression diagnosis kit monitors the concentration of D-serine in the cerebrospinal fluid of the subject to determine whether the subject has depression.
- the concentration of D-serine in the cerebrospinal fluid of the subject is lower than the normal value of 51%, the subject is judged to have depression.
- the depression diagnosis kit monitors the concentration of D-serine in the cerebrospinal fluid of the subject to determine the severity of depression in the subject.
- the depression is moderate depression and above.
- the present invention also provides a diagnostic kit for depression, which monitors the concentration of D-serine in the cerebrospinal fluid of the subject to determine whether the subject has depression.
- the kit includes a D-serine assay buffer, a probe, a D-serine enzyme mixture, a developer enzyme mixture, and a D-serine standard.
- the concentration of D-serine in the cerebrospinal fluid of the subject is detected by detecting the fluorophore formed by the reaction of the oxidized intermediate product of D-serine metabolism with the probe.
- the invention also provides the application of D-serine in the preparation of a medicament for treating depression.
- the present invention finds that D-serine is closely related to depression by studying metabolic substances in abnormal lesions in the brain tissue of patients with depression. Therefore, it is proposed for the first time to apply D-serine as a marker to the field related to the preparation of a diagnostic kit for depression To overcome the shortcomings of the unobjective diagnosis of the indicators used in the diagnosis of depression, and thus provide a new and more accurate objective diagnosis standard for the diagnosis of later depression, and further provide a diagnosis of depression A new way of thinking.
- the depression diagnosis kit provided by the invention can quickly and accurately detect the concentration of D-serine in the cerebrospinal fluid of the subject, thereby effectively and accurately determining whether the subject has depression and the severity of depression.
- D-serine provided in the present invention in the preparation of a medicament for treating depression can increase the excitability of neurons in related brain regions through the release of D-serine, thereby improving depression-like behavior.
- FIG. 1A is a graph showing the results of successful immunohistochemistry of the transgenic animal provided in Example 1 of the present invention.
- 1B is a graph showing the results of the time spent by mice in each group provided in Example 1 of the present invention.
- 1C is a graph showing the interaction time between each group of mice and strange mice provided in Example 1 of the present invention.
- 1D is a graph showing the results of the immobility incubation period of the mice in each group provided in Example 1 of the present invention.
- Example 2 is a graph showing the ability of mouse glial cells to secrete D-serine in each group provided in Example 2 of the present invention.
- the numerical range “a to b” represents an abbreviated representation of any combination of real numbers between a and b, where a and b are both real numbers.
- the numerical range “6-22” means that all real numbers between “6-22” have been listed in this article, and "6-22" is just an abbreviated representation of these numerical combinations.
- the form of the lower limit and the upper limit of the "range" disclosed in the present invention may be one or more lower limits and one or more upper limits, respectively.
- each reaction or operation step may be performed sequentially or in order.
- the reaction methods herein are performed sequentially.
- Depression is also known as depressive disorder, with a significant and persistent mood depression as its main clinical feature, and it is the main type of mood disorder. Clinically, it can be seen that the depressed mood is not commensurate with their situation.
- the depression of emotions can range from depression to grief, inferiority and depression, even pessimism, and suicide attempts or behaviors; even stiffness; some cases have obvious anxiety and motor agitation; In severe cases, mental symptoms such as hallucinations and delusions may occur. Therefore, objective and accurate diagnosis of depression is the first condition for clinical and psychological treatment.
- D-serine is an endogenous brain information co-transmission substance. Its molecular formula is C3H7NO3, molecular weight is 105.09, and its chemical structural formula is:
- the present invention takes depression model mice as an object to study the relationship between the D-serine content in cerebrospinal fluid of normal mice and model mice and depression, and the results show that the level of D-serine in the depression model mouse group is relatively high. The normal group declined.
- the present invention provides the use of D-serine as a marker in the preparation of a diagnostic kit for depression.
- the present invention finds that D-serine is closely related to depression by studying metabolic substances in abnormal lesions in the brain tissue of patients with depression. Therefore, it is proposed for the first time to apply D-serine as a marker to the field related to the preparation of a diagnostic kit for depression To overcome the shortcomings of the unobjective diagnosis of the indicators used in the diagnosis of depression, and thus provide a new and more accurate objective diagnosis standard for the diagnosis of later depression, and further provide a diagnosis of depression A new way of thinking.
- test sample of the depression diagnosis kit is cerebrospinal fluid.
- Cerebrospinal fluid is a colorless and transparent liquid produced by the choroid plexus in the ventricle. It circulates on the surface of the brain and spinal cord, and is related to the systemic circulation through the internal cerebral venous system.
- the main functions are: 1 to protect the brain and spinal cord from external shock damage; 2 to regulate changes in intracranial pressure; 3 to supply nutrients to the brain and spinal cord and to transport away metabolites; 4 to regulate the alkali reserve of the nervous system and maintain normal PH value.
- cerebrospinal fluid will also undergo various changes.
- the present invention is based on the current cerebrospinal fluid is generally used for the examination of nervous system diseases, creatively using cerebrospinal fluid as a detection sample of mental illness depression, can accurately and objectively diagnose depression.
- the depression diagnosis kit determines whether the subject has depression by monitoring the concentration of D-serine in the cerebrospinal fluid of the subject.
- the subject when the concentration of D-serine in the cerebrospinal fluid of the subject is lower than 51% of the normal value, the subject is judged to have depression.
- the concentration of D-serine markers in the cerebrospinal fluid detected by the diagnostic kit for depression is lower than the normal value of 51%, and it is reasonable to make a more objective diagnosis of depression.
- the normal concentration of D-serine in a typical cerebrospinal fluid is the concentration of D-serine in the cerebrospinal fluid of a non-depressed population measured by conventional measurement methods.
- the depression diagnosis kit monitors the concentration of D-serine in the cerebrospinal fluid of the subject to determine the severity of depression in the subject.
- the depression is moderate depression and above.
- Taking the value of the concentration of D-serine in the cerebrospinal fluid of the subject as an indicator of the severity of depression can better reflect the objectivity of the diagnosis or help to improve the accuracy of the diagnosis.
- D-serine as a marker can not only be applied in the preparation of a diagnostic kit for depression. It can also be used in the field of evaluating the efficacy of depression, for evaluating the therapeutic effect of related depression drugs. Therefore, the application of D-serine as a marker also belongs to the protection scope of the present invention.
- the present invention also provides a diagnostic kit for depression, which monitors the concentration of D-serine in the cerebrospinal fluid of the subject to determine whether the subject has depression.
- the depression diagnosis kit provided by the invention can quickly and accurately detect the concentration of D-serine in the cerebrospinal fluid of the subject, thereby effectively and accurately determining whether the subject has depression and the severity of depression.
- the kit includes D-serine assay buffer, probe, D-serine enzyme mixture, developer enzyme mixture, and D-serine standard.
- the concentration of D-serine in the cerebrospinal fluid of the subject is detected by detecting the fluorophore formed by the reaction of the oxidized intermediate product of D-serine metabolism with the probe.
- the present invention proposes the use of D-serine as a marker in the diagnosis or evaluation of therapeutic effects of depression, for example, the use of D-serine as a marker in the preparation of a kit for diagnosis or evaluation of depression, which is easy to understand and corresponding Relevant reagents or antibodies that can detect the concentration or level of D-serine can be used to prepare a diagnostic kit for depression diagnosis or curative effect evaluation, which also belongs to the protection scope of the present invention.
- the present invention first proposes the application of D-serine as a marker in the preparation of a kit for diagnosis or evaluation of depression. Therefore, as long as it is based on this application, all kits used for the diagnosis or evaluation of the efficacy of depression, as long as it uses D-serine as a marker to detect the level of D-serine in the sample, is within the protection scope of the present invention.
- the invention also provides the application of D-serine in the preparation of a medicament for treating depression.
- the release of D-serine can increase the excitability of neurons in related brain regions, thereby improving depression-like behavior.
- D-serine is closely related to depression by studying metabolic substances of abnormal lesions in the brain tissue of patients with depression. Therefore, it is proposed for the first time to apply D-serine as a marker to the preparation of a diagnostic kit for depression In the field of depression, overcoming the shortcomings of the unobjective diagnosis of the indicators used in the diagnosis process of depression, and thus providing a new and more accurate objective diagnosis standard for the diagnosis of later depression, and further diagnosis of depression Provides a new idea.
- the experimental animals, drugs and reagents used in the embodiments of the present invention are all from regular and easy-to-purchase channels:
- D-serine assay buffer, probe, D-serine enzyme mixture, developer enzyme mixture and D-serine standard products were purchased from Kasma Mall; tamoxifen was purchased from sigma; mice were purchased from Beijing Vital Lihua Laboratory Animal Technology Limited company; microplate reader was purchased from biotek.
- this embodiment establishes a rodent depression animal model that can be induced in adulthood.
- tamoxifen-induced transgenic animals start to move earlier than other mice, indicating their depression-like behavior.
- the D-serine level was detected by the following method:
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Abstract
Description
Claims (10)
- D-丝氨酸作为标志物在制备抑郁症诊断试剂盒中的应用。
- 根据权利要求1所述的应用,其特征在于,所述抑郁症诊断试剂盒的检测样本为脑脊液。
- 根据权利要求2所述的应用,其特征在于,所述抑郁症诊断试剂盒通过监测受试者脑脊液中D-丝氨酸的浓度来判断受试者是否患有抑郁症。
- 根据权利要求3所述的应用,其特征在于,当受试者脑脊液中D-丝氨酸的浓度低于正常值51%时,判断所述受试者患有抑郁症。
- 根据权利要求3所述的应用,其特征在于,所述抑郁症诊断试剂盒通过监测受试者脑脊液中D-丝氨酸的浓度来判断受试者患有抑郁症的严重程度。
- 根据权利要求1-5任一项所述的应用,其特征在于,所述抑郁症为中度抑郁症及中度以上的抑郁症。
- 一种抑郁症诊断试剂盒,其特征在于,所述抑郁症诊断试剂盒通过监测受试者脑脊液中D-丝氨酸的浓度来判断受试者是否患有抑郁症。
- 根据权利要求7所述的抑郁症诊断试剂盒,其特征在于,所述试剂盒包括D-丝氨酸测定缓冲液、探针、D-丝氨酸酶混合物、显影剂酶混合物和D-丝氨酸标准。
- 根据权利要求8所述的抑郁症诊断试剂盒,其特征在于,通过检测被氧化后的D-丝氨酸代谢中间产物与探针反应形成的荧光团来检测受试者脑脊液中D-丝氨酸的浓度。
- D-丝氨酸在制备治疗抑郁症的药物中的应用。
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CN109444433A (zh) * | 2018-12-18 | 2019-03-08 | 深圳先进技术研究院 | D-丝氨酸作为标志物在制备抑郁症诊断试剂盒中的应用及抑郁症诊断试剂盒 |
CN114544821B (zh) * | 2020-11-24 | 2023-10-24 | 重庆医科大学 | 检测血浆中磷脂酰乙醇胺(36:4)的试剂在制备抑郁症检测试剂盒中的用途 |
CN114544826B (zh) * | 2020-11-24 | 2023-12-08 | 重庆医科大学 | 检测血浆中组氨酸的试剂在制备抑郁症检测试剂盒中的用途 |
CN114544822B (zh) * | 2020-11-24 | 2023-10-24 | 重庆医科大学 | 检测血浆中溶血磷脂酰胆碱(22:0)的试剂在制备抑郁症检测试剂盒中的用途 |
CN114544790B (zh) * | 2020-11-24 | 2023-10-24 | 重庆医科大学 | 检测血浆中溶血磷脂酰乙醇胺(22:5)的试剂在制备抑郁症检测试剂盒中的用途 |
CN114544825A (zh) * | 2020-11-24 | 2022-05-27 | 重庆医科大学 | 检测血浆中溶血磷脂酰胆碱(16:1)的试剂在制备抑郁症检测试剂盒中的用途 |
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