CN112121046A - 来那度胺在治疗主动脉夹层中的制药用途 - Google Patents
来那度胺在治疗主动脉夹层中的制药用途 Download PDFInfo
- Publication number
- CN112121046A CN112121046A CN202011216364.5A CN202011216364A CN112121046A CN 112121046 A CN112121046 A CN 112121046A CN 202011216364 A CN202011216364 A CN 202011216364A CN 112121046 A CN112121046 A CN 112121046A
- Authority
- CN
- China
- Prior art keywords
- lenalidomide
- aortic dissection
- aortic
- dissection
- treatment
- 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
- 208000002251 Dissecting Aneurysm Diseases 0.000 title claims abstract description 50
- 206010002895 aortic dissection Diseases 0.000 title claims abstract description 50
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960004942 lenalidomide Drugs 0.000 title claims abstract description 41
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 23
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 23
- 230000000694 effects Effects 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 9
- 210000005119 human aortic smooth muscle cell Anatomy 0.000 abstract description 12
- 210000000709 aorta Anatomy 0.000 abstract description 10
- 101800000733 Angiotensin-2 Proteins 0.000 abstract description 9
- 102400000345 Angiotensin-2 Human genes 0.000 abstract description 9
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 abstract description 9
- 210000001519 tissue Anatomy 0.000 abstract description 7
- 230000004913 activation Effects 0.000 abstract description 4
- 230000001413 cellular effect Effects 0.000 abstract description 4
- 230000002496 gastric effect Effects 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 208000031816 Pathologic Dilatation Diseases 0.000 abstract description 2
- 230000032459 dedifferentiation Effects 0.000 abstract description 2
- 238000010172 mouse model Methods 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 7
- 238000001514 detection method Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 210000002376 aorta thoracic Anatomy 0.000 description 4
- AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical compound NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 210000004177 elastic tissue Anatomy 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000007805 zymography Methods 0.000 description 3
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
- 102100036732 Actin, aortic smooth muscle Human genes 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 2
- 101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 2
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 2
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 2
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 102100031013 Transgelin Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000007348 cell dedifferentiation Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 102100033620 Calponin-1 Human genes 0.000 description 1
- 102000002664 Core Binding Factor Alpha 2 Subunit Human genes 0.000 description 1
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 1
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000001826 Marfan syndrome Diseases 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 206010049771 Shock haemorrhagic Diseases 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
来那度胺在治疗主动脉夹层中的制药用途，涉及在心血管领域。动物水平，在主动脉夹层小鼠模型中，给予来那度胺灌胃后，可改善主动脉病理性扩张，降低死亡率及主动脉夹层的发生率，同时可明显抑制主动脉夹层小鼠主动脉组织基质金属蛋白酶（MMP）的过度激活。细胞水平，给予来那度胺处理后，可抑制血管紧张素2诱导的人主动脉平滑肌细胞（HASMCs）的MMP活性升高及去分化。本发明开拓了来那度胺的一个新的应用领域，提出主动脉夹层新的防治方法，对于主动脉夹层的新型药物的研制提供了新途径。
Description
技术领域
本发明属于主动脉夹层防治技术领域，具体涉及来那度胺在制备治疗主动脉夹层（AD）药物中的应用。
背景技术
主动脉夹层（Aortic dissection，AD）是尚未有有效药物治疗的高致命率疾病，是危及人类健康安全的常见疾病之一。主动脉内膜在某些病理因素下局部撕裂，在血液冲击作用下，逐步剥离、扩展，并且在动脉内形成真假两腔，当主动脉夹层破裂，便会造成失血性休克、心包填塞等严重后果，甚至猝死。AD发生最常见的年龄在65-75岁之间，主要危险因素包括高血压，血脂异常及结缔组织遗传疾病，如马凡氏综合症。AD发病后48小时内的病死率为50%-68%，3个月内的病死率为90%，每年每10万人中有35例病例。因此，AD具有进展快、病情复杂、致死率高的特点，找寻新的有效的治疗主动脉夹层（AD）的方法是临床上有效降低其高致死率的关键。
血管平滑肌细胞表型转化被认为是参与主动脉夹层发生发展的重要机制之一。生理情况下，血管平滑肌细胞保持静止状态，表现出一种分化的、收缩的表型，这是维持正常血流和血压所必需的。但当血管损伤或局部环境改变时，血管平滑肌细胞由分化状态向去分化状态转变，即收缩型平滑肌细胞转化为合成型平滑肌细胞，其特征是细胞增殖迁移、细胞外基质合成、基质金属蛋白酶过度激活以及炎症细胞因子增加等。研究血管平滑肌细胞表型转化的调控分子及相关机制，有利于发现 AD 的新干预靶点。
来那度胺是一种免疫调节药物（Lenalidomide，LEN），在多发性骨髓瘤和骨髓增生异常综合症的治疗中已建立并得到认可。作用方式包括免疫调节、抗血管生成、抗炎和抗增殖等作用。文献报道，来那度胺对骨髓瘤细胞有直接的细胞毒性作用，并且能够诱导细胞凋亡。它还能够通过抑制血管内皮生长因子（Vascular endothelial growth factor, VEGF）的分泌来减少血管生成，调节骨髓微血管并抑制骨髓瘤细胞的生长和增殖。并且来那度胺可促进转录因子RUNX1表达，调节巨核细胞分化而改善骨髓增生异常综合症。但是来那度胺是否能够抑制主动脉夹层的发生及其机制目前尚未有任何相关的研究和报道。
发明内容
解决的技术问题：本发明提供来那度胺在治疗主动脉夹层中的制药用途，有效抑制主动脉夹层发生。该方法包含主动脉夹层模型小鼠灌胃给予来那度胺，以及利用来那度胺处理人主动脉平滑肌细胞（HASMCs）。
技术方案: 来那度胺在制备降低主动脉夹层小鼠主动脉组织基质金属蛋白酶（MMP）活性药物中的应用。
来那度胺在制备治疗主动脉夹层药物中的应用。
治疗主动脉夹层药物，有效成分包括来那度胺。
有益效果：主动脉夹层模型小鼠灌胃给予来那度胺后，可有效抑制主动脉病理性扩张，降低死亡率及主动脉夹层的发生率，同时可减轻主动脉夹层小鼠主动脉组织基质金属蛋白酶（MMP）的过度激活，缓解细胞外弹性纤维降解；人主动脉平滑肌细胞（HASMCs）在血管紧张素2刺激下，给予来那度胺后，可抑制MMP活性升高及细胞去分化。
附图说明
图1为主动脉夹层模型鼠灌胃给予来那度胺后的疗效图，采用3周龄的C57BL/6J雄性小鼠，给予β-氨基丙腈（BAPN）饮水4周，诱导主动脉夹层发生，同时灌胃给予来那度胺和对照溶剂。其中A：分离小鼠主动脉并量化升主动脉/降主动脉/胸主动脉的最大直径，检测主动脉病理性扩张，标尺为5 mm，n=6-9，*P<0.05， ***P<0.001；B：检测小鼠存活率，n=6-9；C：检测小鼠主动脉夹层发生率，n=6-9。
图2为小鼠主动脉组织基质金属蛋白酶（MMP）活性检测示意图，分离小鼠主动脉，组织包埋剂OCT包埋，冰冻切片后原位酶谱法检测MMP活性，标尺为40 μm。
图3为细胞水平给予来那度胺处理后基质金属蛋白酶活性检测示意图，人主动脉平滑肌细胞中，无血清培养基饥饿24小时，再给予血管紧张素2（1 μM）及来那度胺（10 μM）处理24小时，原位酶谱法检测基质金属蛋白酶活性，标尺为40 μm ，n=3，*P<0.05，**P<0.01。
图4为细胞水平给予来那度胺处理后，平滑肌细胞收缩型/合成型标记物检测示意图，人主动脉平滑肌细胞中，无血清培养基饥饿24小时，再给予血管紧张素2（1 μM）及来那度胺（10 μM）处理24小时，提取细胞RNA。其中A：检测人主动脉平滑肌细胞收缩型标志物（CNN1、TAGLN、ACTA2）的表达，n=4，**P<0.01，***P<0.001 vs 对照组，###P<0.001 vs 血管紧张素2；B：检测人主动脉平滑肌细胞合成型标志物（OPN、KLF4、MMP2、MMP9）的表达，n=4，**P<0.01，***P<0.001 vs 对照组，##P<0.01，###P<0.001 vs 血管紧张素2。
具体实施方式
下面的实施例可使本专业技术人员更全面地理解本发明，但不以任何方式限制本发明。实例中所用来那度胺为市售产品，购买于selleck.cn。
实施例1：
动物水平，来那度胺降低主动脉夹层发生率，改善主动脉弹性纤维完整性及组织形态。
为了探究来那度胺对主动脉夹层的调节作用，我们选用了SPF级3周雄性C57BL/6J小鼠（购于南京医科大学医药实验动物中心），随机分为3组：对照组，主动脉夹层模型组（0.25%BAPN饮水，28天）及主动脉夹层小鼠灌胃给予来那度胺（30 mg/kg/天，28天）组。单纯BAPN饮水的主动脉夹层模型鼠，其主动脉出现明显的病理性扩张，升主动脉/降主动脉/胸主动脉直径约为对照组的1.5倍（图 1：A），死亡率及主动脉夹层发生率较对照组显著增加，而主动脉夹层小鼠在灌胃给予来那度胺（30 mg/kg/天）后，主动脉直径的扩张、小鼠死亡率及主动脉夹层发生率均得到抑制，表明来那度胺可抑制主动脉夹层的发生。
已知基质金属蛋白酶（MMP）过度活化使胞外基质过度降解，促使血管弹性纤维降解并加速平滑肌细胞增殖迁移，广泛参与主动脉夹层的发生。所以我们通过原位酶谱法检测了小鼠主动脉中MMP的活性，发现主动脉夹层小鼠血管中MMP荧光强度显著增加，而来那度胺处理组血管MMP活性降低，细胞外弹性膜降解得到抑制（图 2），表明来那度胺可通过抑制MMP活性改善主动脉弹性纤维完整性及组织形态。
实施例2：
细胞水平，给予来那度胺可抑制血管紧张素2诱导的人主动脉平滑肌细胞的去分化。
原位酶谱实验检测发现，在人主动脉平滑肌细胞中给予血管紧张素2处理后，基质金属蛋白酶活性明显增加；在此基础上，给予来那度胺后，基质金属蛋白酶活性受到抑制（图 3），RT-PCR检测发现，来那度胺处理可减轻血管紧张素2诱导的平滑肌细胞收缩性标志物CNN1， TAGLN，ACTA2 的表达降低及合成型标志物OPN、KLF4、MMP2、MMP9的表达增加（图4），抑制平滑肌细胞去分化。上述结果提示，来那度胺可通过抑制平滑肌细胞的表型转化，延缓主动脉夹层疾病进程。
Claims (3)
1.来那度胺在制备降低主动脉夹层小鼠主动脉组织基质金属蛋白酶（MMP）活性药物中的应用。
2.来那度胺在制备治疗主动脉夹层药物中的应用。
3.治疗主动脉夹层药物，其特征在于有效成分包括来那度胺。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011216364.5A CN112121046A (zh) | 2020-11-04 | 2020-11-04 | 来那度胺在治疗主动脉夹层中的制药用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011216364.5A CN112121046A (zh) | 2020-11-04 | 2020-11-04 | 来那度胺在治疗主动脉夹层中的制药用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112121046A true CN112121046A (zh) | 2020-12-25 |
Family
ID=73852133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011216364.5A Pending CN112121046A (zh) | 2020-11-04 | 2020-11-04 | 来那度胺在治疗主动脉夹层中的制药用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112121046A (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112891368A (zh) * | 2021-01-26 | 2021-06-04 | 南京医科大学 | 硫化氢供体的制药用途 |
| CN116370444A (zh) * | 2023-03-07 | 2023-07-04 | 首都医科大学附属北京安贞医院 | 一种辅酶q10用于制备预防及治疗主动脉夹层药物的用途 |
-
2020
- 2020-11-04 CN CN202011216364.5A patent/CN112121046A/zh active Pending
Non-Patent Citations (3)
| Title |
|---|
| LUCIA MESSINGEROVÁ等: "Lenalidomide treatment induced the normalization of marker protein levels in blood plasma of patients with 5q-myelodysplastic syndrome", 《GENERAL PHYSIOLOGY AND BIOPHYSICS》 * |
| 李金等: "基质金属蛋白酶2,9与主动脉夹层发病关系的研究进展", 《广东医学》 * |
| 高斌斌: "沙利度胺抑制兔实验性腹主动脉瘤生长的研究", 《中国博士学位论文全文数据库医药卫生科技辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112891368A (zh) * | 2021-01-26 | 2021-06-04 | 南京医科大学 | 硫化氢供体的制药用途 |
| CN116370444A (zh) * | 2023-03-07 | 2023-07-04 | 首都医科大学附属北京安贞医院 | 一种辅酶q10用于制备预防及治疗主动脉夹层药物的用途 |
| CN116370444B (zh) * | 2023-03-07 | 2023-12-29 | 首都医科大学附属北京安贞医院 | 一种辅酶q10用于制备预防及治疗主动脉夹层药物的用途 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hladik et al. | Effects of ionizing radiation on the mammalian brain | |
| Soltany | Postoperative peritoneal adhesion: an update on physiopathology and novel traditional herbal and modern medical therapeutics | |
| Wang et al. | Activation of PPARγ is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress | |
| Krishnan et al. | Molecular pathways mediating the anti-inflammatory effects of calcitriol: implications for prostate cancer chemoprevention and treatment | |
| Seyedzadeh et al. | Study of curcumin immunomodulatory effects on reactive astrocyte cell function | |
| Hagenlocher et al. | Cinnamon extract reduces symptoms, inflammatory mediators and mast cell markers in murine IL-10−/− colitis | |
| CN112121046A (zh) | 来那度胺在治疗主动脉夹层中的制药用途 | |
| US9669005B2 (en) | Use of naringenin in preparing drugs for preventing and/or treatment abdominal aortic aneurysm | |
| RU2681930C2 (ru) | Применение андрографолида в получении фармацевтического препарата для лечения воспалительного заболевания кишечника, микропеллета с андрографолидом для целенаправленной доставки в кишечник и способ ее получения | |
| Li et al. | Dihydromyricetin ameliorates memory impairment induced by acute sleep deprivation | |
| Kim et al. | Oral administration of 3, 3’-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice | |
| KR102166907B1 (ko) | 데커시놀 안젤레이트를 유효성분으로 포함하는 대장염 예방 또는 치료 조성물 | |
| Zhang et al. | Potential medication treatment according to pathological mechanisms in abdominal aortic aneurysm | |
| Sun et al. | MiR-325-3p promotes locomotor function recovery in rats with spinal cord injury via inhibiting the expression of neutrophil elastase | |
| CN113712960B (zh) | R-酮咯酸在防治主动脉夹层和主动脉瘤中的应用 | |
| CN109364048A (zh) | 根皮素在制备预防和治疗结肠炎药物中的应用 | |
| CN111190019B (zh) | 胆碱转运蛋白2的医药用途 | |
| CN113069459A (zh) | 索尼德吉在治疗主动脉夹层中的制药用途 | |
| AU2020364192A1 (en) | Gastrointestinal health composition | |
| CN112755015A (zh) | Pt2385在制备防治肺动脉高压的药物中的应用 | |
| Karthik et al. | Rosmarinic acid treatment alleviates fibrotic changes in the myocardium induced in a rat model of insulin resistance | |
| TWI593420B (zh) | 用於減緩關節炎的組合物及其醫藥品、製造方法與應用 | |
| CA3002679A1 (en) | Thylakoid extract composition and formulation for the treatment of inflammatory bowel disease | |
| Jhun et al. | The chicken combs extract alleviates pain and cartilage degradation in rat model osteoarthritis | |
| Islam et al. | The comparison and efficacy of nifedipine and tamsulosin for the management of lower ureteric stones |
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: 20201225 |