CN116019799A - 一种验证布美他尼能改善精神分裂症认知损伤的实验方法 - Google Patents
一种验证布美他尼能改善精神分裂症认知损伤的实验方法 Download PDFInfo
- Publication number
- CN116019799A CN116019799A CN202211401957.8A CN202211401957A CN116019799A CN 116019799 A CN116019799 A CN 116019799A CN 202211401957 A CN202211401957 A CN 202211401957A CN 116019799 A CN116019799 A CN 116019799A
- Authority
- CN
- China
- Prior art keywords
- rats
- model group
- schizophrenia
- bumetanide
- cognitive impairment
- 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.)
- Pending
Links
- 201000000980 schizophrenia Diseases 0.000 title claims abstract description 32
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960004064 bumetanide Drugs 0.000 title claims abstract description 28
- 208000028698 Cognitive impairment Diseases 0.000 title claims abstract description 25
- 208000010877 cognitive disease Diseases 0.000 title claims abstract description 25
- 238000002474 experimental method Methods 0.000 title claims abstract description 22
- 241000700159 Rattus Species 0.000 claims abstract description 71
- 108091006620 SLC12A2 Proteins 0.000 claims abstract description 18
- 108091006634 SLC12A5 Proteins 0.000 claims abstract description 18
- 102100034243 Solute carrier family 12 member 2 Human genes 0.000 claims abstract description 18
- 102100034250 Solute carrier family 12 member 5 Human genes 0.000 claims abstract description 18
- 230000000698 schizophrenic effect Effects 0.000 claims abstract description 16
- 230000014509 gene expression Effects 0.000 claims abstract description 10
- 238000003119 immunoblot Methods 0.000 claims abstract description 6
- 241000699670 Mus sp. Species 0.000 claims description 23
- 239000000902 placebo Substances 0.000 claims description 7
- 229940068196 placebo Drugs 0.000 claims description 7
- 230000035935 pregnancy Effects 0.000 claims description 7
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 6
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 6
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 6
- 102000004889 Interleukin-6 Human genes 0.000 claims description 6
- 108090001005 Interleukin-6 Proteins 0.000 claims description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 238000010253 intravenous injection Methods 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 5
- 238000002965 ELISA Methods 0.000 claims description 4
- 230000005934 immune activation Effects 0.000 claims description 4
- 238000012360 testing method Methods 0.000 claims description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 3
- 230000010100 anticoagulation Effects 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000007928 intraperitoneal injection Substances 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 239000002504 physiological saline solution Substances 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 210000003462 vein Anatomy 0.000 claims description 3
- 230000006998 cognitive state Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 230000006872 improvement Effects 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 4
- 230000000971 hippocampal effect Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000007370 cognitive improvement Effects 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 238000000537 electroencephalography Methods 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
Images
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明提供一种验证布美他尼能改善精神分裂症认知损伤的实验方法,其特征在于包括以下步骤:步骤一:制备精神分裂症模型组大鼠和对照组大鼠;步骤二:通过免疫印迹实验验证精神分裂症模型组大鼠存在NKCC1/KCC2表达失衡;步骤三:验证布美他尼能改善精神分裂症模型组大鼠认知损伤。根据多次实验发现,精神分裂症模型组大鼠存在显著NKCC1/KCC2失衡,而NKCC1/KCC2系统调节药物布美他尼可显著改善精神分裂症模型组大鼠的认知损伤,且起效周期短、改善效果高效、稳定,证实了布美他尼在精神分裂症认知损伤中的治疗价值。
Description
技术领域
本发明属于精神病研究技术领域,具体涉及一种验证布美他尼能改善精神分裂症认知损伤的实验方法。
背景技术
精神分裂症患者临床症状包括阳性症状、阴性症状、认知损伤,其中认知损伤是影响患者社会功能恢复的主要限制因素。而现有的抗精神病药物可显著改善患者的阳性和阴性症状,但对认知损伤的改善效果并不理想。这些药物治疗无效的根源在于导致认知缺陷的分子机制不明、进而缺乏针对认知损伤的药物治疗。
前期本人制备精神分裂症大鼠模型,发现模型大鼠成年期海马NKCC1表达增加,KCC2表达降低,存在NKCC1/KCC2失衡现象,本发现提示NKCC1/KCC2失衡有可能作为精神分裂症认知损伤的药物研发靶点。而布美他尼作为NKCC1/KCC2系统调节药物,本人猜想其可显著改善精神分裂症模型大鼠的认知损伤,故而需要一种实验进行证实。
发明内容
本发明的目的是针对现有技术的不足,提供一种验证布美他尼能改善精神分裂症认知损伤的实验方法,具体方案如下:
一种验证布美他尼能改善精神分裂症认知损伤的实验方法,其包括以下步骤:
步骤一:制备精神分裂症模型组大鼠和对照组大鼠;
步骤二:通过免疫印迹实验验证精神分裂症模型组大鼠存在NKCC1/KCC2表达失衡;
步骤三:验证布美他尼能改善精神分裂症模型组大鼠认知损伤。
基于上述,所述步骤一包括以下操作步骤:
步骤1:母体处理:模型组孕鼠在怀孕第9天一侧尾静脉注射10mg/kg的Poly I:C,对照组孕鼠在怀孕第9天一侧尾静脉注射等体积生理盐水处理;
步骤2:母体检测:3小时后在模型组孕鼠、对照组孕鼠的另一侧尾静脉分别抽取约1ml血液,并添加EDTA抗凝,4℃、1000g、离心15min,取上层血清,ELISA检测二者血浆炎症因子IL-1β、IL-6、TNF-α含量,当结果显示模型组孕鼠相对于对照组孕鼠的炎症因子IL-1β、IL-6、TNF-α水平显著升高时,提示母体免疫激活模型制备成功;
步骤3:将模型组孕鼠、对照组孕鼠的子代雄性大鼠正常饲养至成年期,即为精神分裂症模型组大鼠和对照组大鼠。
基于上述,所述步骤三包括以下操作步骤:
步骤1:将精神分裂症模型组大鼠分为两组,给予其中一组连续7天腹腔注射布美他尼(15 mg/kg),以同样注射方式给予另外一组以及对照组大鼠安慰剂处理;
步骤2:用新物体识别实验评估三组大鼠的认知状态;
步骤3:对三组大鼠进行脑电检测。
本发明相对现有技术具有突出的实质性特点和显著的进步,具体地说,本发明具有以下优点:
根据多次实验发现,精神分裂症模型组大鼠存在显著NKCC1/KCC2失衡,而NKCC1/KCC2系统调节药物布美他尼可显著改善精神分裂症模型组大鼠的认知损伤,且起效周期短、改善效果高效、稳定,证实了布美他尼在精神分裂症认知损伤中的治疗价值。
附图说明
图1是本发明中ELISA检测孕期母体免疫激活状态的数据分析图。
图2是本发明中通过免疫印迹实验检测精神分裂症模型组大鼠和对照组大鼠NKCC1/KCC2表达水平的数据分析图。
图3是本发明中对两组精神分裂症模型组大鼠分别给予安慰剂、布美他尼以及对照组大鼠给予安慰剂后进行新物体识别实验数据分析图。
图4是是本发明中对两组精神分裂症模型组大鼠分别给予安慰剂、布美他尼以及对照组大鼠给予安慰剂后进行脑电检测的数据分析图。
具体实施方式
下面通过具体实施方式,对本发明的技术方案做进一步的详细描述。
实施例
本发明提供一种验证布美他尼能改善精神分裂症认知损伤的实验方法,其包括以下步骤:
步骤一:制备精神分裂症模型组大鼠和对照组大鼠;
步骤二:通过免疫印迹实验验证精神分裂症模型组大鼠存在NKCC1/KCC2表达失衡(如图2A-B所示,免疫印迹检测海马NKCC1和KCC2蛋白表达,并统计分析,结果发现,相对于对照组大鼠来说,精神分裂症模型组大鼠海马NKCC1表达显著增加、KCC2表达降低,存在NKCC1/KCC2失衡);
步骤三:验证布美他尼能改善精神分裂症模型组大鼠认知损伤。
基于上述,所述步骤一包括以下操作步骤:
步骤1:母体处理:模型组孕鼠在怀孕第9天一侧尾静脉注射10mg/kg的Poly I:C,对照组孕鼠在怀孕第9天一侧尾静脉注射等体积生理盐水处理;
步骤2:母体检测:3小时后在模型组孕鼠、对照组孕鼠的另一侧尾静脉分别抽取约1ml血液,并添加EDTA抗凝,4℃、1000g、离心15min,取上层血清,ELISA检测二者血浆炎症因子IL-1β、IL-6、TNF-α含量,当结果显示模型组孕鼠相对于对照组孕鼠的炎症因子IL-1β、IL-6、TNF-α水平显著升高时(如图1A-C所示),提示母体免疫激活模型制备成功;
步骤3:将模型组孕鼠、对照组孕鼠的子代雄性大鼠正常饲养至成年期,即为精神分裂症模型组大鼠和对照组大鼠。
基于上述,所述步骤三包括以下操作步骤:
步骤1:将精神分裂症模型组大鼠分为两组,给予其中一组连续7天腹腔注射布美他尼(15 mg/kg),以同样注射方式给予另外一组以及对照组大鼠安慰剂处理;
步骤2:用新物体识别实验评估三组大鼠的认知状态(如图3所示,新物体识别实验:第1天,让大鼠在检测装置中适应30分钟熟悉环境;第2天训练期,在装置中放置2个一样的物体,让大鼠探索10分钟,随后放回笼内,2小时之后进行测试,将装置内一个物体用新物体替代,再次让大鼠进行探索,记录大鼠接触新、旧物体的时间,分别记录为T2、T1,通过T2/(T1+T2)计算大鼠对新物体的偏爱,利用啮齿类动物喜新厌旧的特性,评估大鼠的记忆,反映认知状态。结果显示,相比于给予安慰剂处理的精神分裂症模型组大鼠,给予布美他尼处理的精神分裂症模型组大鼠增加了其对新物体的探究偏爱,提示认知改善);
步骤3:对三组大鼠进行脑电检测(脑电检测大鼠的认知功能:脑立体定位大鼠右侧海马区,在大鼠海马区放置16通道电极监测海马区场电以及Gamma波信号。结果显示,相比于给予安慰剂处理的精神分裂症模型组大鼠,给予布美他尼处理可改善精神分裂症模型组大鼠海马区场电信号以及Gamma波信号,提示认知改善)。
根据多次实验发现,精神分裂症模型组大鼠存在显著NKCC1/KCC2失衡,而NKCC1/KCC2系统调节药物布美他尼可显著改善精神分裂症模型组大鼠的认知损伤,且起效周期短、改善效果高效、稳定,证实了布美他尼在精神分裂症认知损伤中的治疗价值。
最后应当说明的是:以上实施例仅用以说明本发明的技术方案而非对其限制;尽管参照较佳实施例对本发明进行了详细的说明,所属领域的普通技术人员应当理解:依然可以对本发明的具体实施方式进行修改或者对部分技术特征进行等同替换;而不脱离本发明技术方案的精神,其均应涵盖在本发明请求保护的技术方案范围当中。
Claims (3)
1.一种验证布美他尼能改善精神分裂症认知损伤的实验方法,其特征在于包括以下步骤:
步骤一:制备精神分裂症模型组大鼠和对照组大鼠;
步骤二:通过免疫印迹实验验证精神分裂症模型组大鼠存在NKCC1/KCC2表达失衡;
步骤三:验证布美他尼能改善精神分裂症模型组大鼠认知损伤。
2.根据权利要求1所述的验证布美他尼能改善精神分裂症认知损伤的实验方法,其特征在于所述步骤一包括以下操作步骤:
步骤1:母体处理:模型组孕鼠在怀孕第9天一侧尾静脉注射10mg/kg的Poly I:C,对照组孕鼠在怀孕第9天一侧尾静脉注射等体积生理盐水处理;
步骤2:母体检测:3小时后在模型组孕鼠、对照组孕鼠的另一侧尾静脉分别抽取约1ml血液,并添加EDTA抗凝,4℃、1000g、离心15min,取上层血清,ELISA检测二者血浆炎症因子IL-1β、IL-6、TNF-α含量,当结果显示模型组孕鼠相对于对照组孕鼠的炎症因子IL-1β、IL-6、TNF-α水平显著升高时,提示母体免疫激活模型制备成功;
步骤3:将模型组孕鼠、对照组孕鼠的子代雄性大鼠正常饲养至成年期,即为精神分裂症模型组大鼠和对照组大鼠。
3.根据权利要求1所述的验证布美他尼能改善精神分裂症认知损伤的实验方法,其特征在于所述步骤三包括以下操作步骤:
步骤1:将精神分裂症模型组大鼠分为两组,给予其中一组连续7天腹腔注射布美他尼(15 mg/kg),以同样注射方式给予另外一组以及对照组大鼠安慰剂处理;
步骤2:用新物体识别实验评估三组大鼠的认知状态;
步骤3:对三组大鼠进行脑电检测。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211401957.8A CN116019799A (zh) | 2022-11-09 | 2022-11-09 | 一种验证布美他尼能改善精神分裂症认知损伤的实验方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211401957.8A CN116019799A (zh) | 2022-11-09 | 2022-11-09 | 一种验证布美他尼能改善精神分裂症认知损伤的实验方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116019799A true CN116019799A (zh) | 2023-04-28 |
Family
ID=86071445
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211401957.8A Pending CN116019799A (zh) | 2022-11-09 | 2022-11-09 | 一种验证布美他尼能改善精神分裂症认知损伤的实验方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116019799A (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090076019A1 (en) * | 2006-10-13 | 2009-03-19 | Mount Sinai Hospital | Methods for treating neurological disorders or damage |
CN102341380A (zh) * | 2009-01-22 | 2012-02-01 | 神经病治疗药物股份有限公司 | 布美他尼、呋塞米、吡咯他尼、佐塞米和托拉塞米类似物、组合物和使用方法 |
US20140066504A1 (en) * | 2012-09-04 | 2014-03-06 | Daryl W. Hochman | Analogs and prodrugs of bumetanide; compositions and methods of use |
US20200405672A1 (en) * | 2019-06-28 | 2020-12-31 | Northwestern University | Methods for treating psychiatric diseases and disorders and the symptoms thereof in a subject by administering an antagonist of the na+-k+-2cl- cation-chloride cotransporter isoform 1 (nkcc1) |
US20210163406A1 (en) * | 2018-04-06 | 2021-06-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Bumetanide Derivatives for the Therapy of Stroke and Other Neurological Diseases/Disorders Involving NKCCs |
-
2022
- 2022-11-09 CN CN202211401957.8A patent/CN116019799A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090076019A1 (en) * | 2006-10-13 | 2009-03-19 | Mount Sinai Hospital | Methods for treating neurological disorders or damage |
CN102341380A (zh) * | 2009-01-22 | 2012-02-01 | 神经病治疗药物股份有限公司 | 布美他尼、呋塞米、吡咯他尼、佐塞米和托拉塞米类似物、组合物和使用方法 |
US20140066504A1 (en) * | 2012-09-04 | 2014-03-06 | Daryl W. Hochman | Analogs and prodrugs of bumetanide; compositions and methods of use |
US20210163406A1 (en) * | 2018-04-06 | 2021-06-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Bumetanide Derivatives for the Therapy of Stroke and Other Neurological Diseases/Disorders Involving NKCCs |
US20200405672A1 (en) * | 2019-06-28 | 2020-12-31 | Northwestern University | Methods for treating psychiatric diseases and disorders and the symptoms thereof in a subject by administering an antagonist of the na+-k+-2cl- cation-chloride cotransporter isoform 1 (nkcc1) |
Non-Patent Citations (10)
Title |
---|
HARAM R. KIM, 等: "Depolarizing GABA(A) current in the prefrontal cortex is linked with cognitive impairment in a mouse model relevant for schizophrenia", SCIENCE ADVANCES, vol. 07, no. 14, pages 5032 * |
REZA RAHMANZADEH,等: "Effect of bumetanide, a selective NKCC1 inhibitor, on hallucinations of schizophrenic patients; a double-blind randomized clinical trial", SCHIZOPHRENIA RESEARCH, vol. 184, pages 145 - 146, XP085060143, DOI: 10.1016/j.schres.2016.12.002 * |
刘鑫垚;等: "精神分裂症认知损害动物模型的研究现状", 首都医科大学学报, vol. 41, no. 01, pages 50 - 54 * |
周亚亚,等: "Na-K-Cl协同转运蛋白研究进展", 现代生物医学进展, vol. 11, no. 15, pages 2996 - 3000 * |
孙福萍: "孕期感染子代精神分裂症大鼠模型γ-氨基丁酸能系统紊乱与行为异常的研究", 中国优秀硕士学位论文全文数据库医药卫生科技辑, no. 12, pages 1 * |
朱少飞;等: "鞘内注射布美他尼对大鼠急性疼痛行为及钠钾氯联合转运蛋白1表达的影响", 实用药物与临床, vol. 18, no. 03, pages 272 - 276 * |
杜艳芳,等: "新物体识别实验应用研究", 科学技术创新, no. 03, pages 1 * |
王佳;等: "Poly I:C母体免疫刺激诱导的子代精神分裂症神经发育动物模型", 心理科学, vol. 38, no. 01, pages 229 - 236 * |
王玉聪;等: "Poly I:C母鼠免疫刺激及母婴分离对子代精神分裂症样行为的影响", 江苏大学学报(医学版), vol. 27, no. 05, pages 379 - 384 * |
马骏,等: "首发精神分裂症患者治疗效果与血清炎性因子水平变化关系研究", 新乡医学院学报, vol. 34, no. 02, pages 113 - 116 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fisher et al. | Stem cell therapy for chronic ischaemic heart disease and congestive heart failure | |
Minneci et al. | Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose | |
Forteza et al. | Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size in Post‐PCI Patients | |
Zhang et al. | Targeting nuclear receptor NR4A1–dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity | |
Newton et al. | Neutrophils infiltrate the spinal cord parenchyma of rats with experimental diabetic neuropathy | |
Wu et al. | The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis | |
Wang et al. | Micro RNA-19a suppresses interleukin-10 in peripheral B cells of patients with diabetic retinopathy | |
Brunton et al. | Suppressed oxytocin neuron responses to immune challenge in late pregnant rats: a role for endogenous opioids | |
Sellnow et al. | Striatal Nurr1 facilitates the dyskinetic state and exacerbates levodopa-induced dyskinesia in a rat model of Parkinson's disease | |
Toedebusch et al. | AMPK agonist AICAR delays the initial decline in lifetime-apex V̇o2 peak, while voluntary wheel running fails to delay its initial decline in female rats | |
CN116019799A (zh) | 一种验证布美他尼能改善精神分裂症认知损伤的实验方法 | |
US20130230499A1 (en) | Cellular blood markers for early diagnosis of als and for als progression | |
WO2020247591A1 (en) | Synchronized cell cycle gene expression test for alzheimer's disease | |
Yu et al. | The G‐protein‐coupled chemoattractant receptor Fpr2 exacerbates neuroglial dysfunction and angiogenesis in diabetic retinopathy | |
Pensa et al. | Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis | |
Iftikhar et al. | A challenging diagnosis of systemic lupus erythematosus with status epilepticus | |
CN116076440B (zh) | 验证wnk1抑制剂在制备治疗认知障碍药物中的应用 | |
Zhao et al. | KCNQ1 G219E and TRPM4 T160M polymorphisms are involved in the pathogenesis of long QT syndrome: A case report | |
AU2022200653A1 (en) | Viral vector for treating autoimmune disease and diabetes and construction method and application thereof | |
CN112195181A (zh) | MiR-29海绵在制备用于治疗2型糖尿病的药物中的应用 | |
Song et al. | Comprehensive Proteomic Analysis of the Differential Expression of 83 Proteins Following Intracortical Microelectrode Implantation | |
CN115399290B (zh) | 一种模拟铁过载导致糖尿病前期阶段症状的小鼠模型建立方法 | |
Zhang et al. | Challenges towards management of CARD9‐deficient patients with phaeohyphomycosis: A case report and case series study | |
Wang et al. | Interleukin‐22 Deficiency Reduces Angiotensin II‐Induced Aortic Dissection and Abdominal Aortic Aneurysm in ApoE‐/‐Mice | |
Feng et al. | Serum response factor promotes axon regeneration following spinal cord transection injury |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20230428 |