CN108815161A - 异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用 - Google Patents
异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用 Download PDFInfo
- Publication number
- CN108815161A CN108815161A CN201811099576.2A CN201811099576A CN108815161A CN 108815161 A CN108815161 A CN 108815161A CN 201811099576 A CN201811099576 A CN 201811099576A CN 108815161 A CN108815161 A CN 108815161A
- Authority
- CN
- China
- Prior art keywords
- isorhynchophylline
- zinc
- deficiency
- cholinergic neuron
- drug
- 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.)
- Granted
Links
- IQSFEAHJUMVILC-UHFFFAOYSA-N Isorhynchophyllic acid Natural products CCC1CN2CCC3(C2CC1C(=COC)C(=O)O)C(=O)Nc4ccccc34 IQSFEAHJUMVILC-UHFFFAOYSA-N 0.000 title claims abstract description 48
- DAXYUDFNWXHGBE-VKCGGMIFSA-N Isorhynchophylline Chemical compound O=C1NC2=CC=CC=C2[C@]11CCN2C[C@H](CC)[C@@H](\C(=C/OC)C(=O)OC)C[C@H]21 DAXYUDFNWXHGBE-VKCGGMIFSA-N 0.000 title claims abstract description 48
- VCNYNWHVJKWJRQ-UHFFFAOYSA-N Isorhynchophylline Natural products CCC1=CN2CCC3(C2CC1C(=COC)C(=O)OC)C(=O)Nc4ccccc34 VCNYNWHVJKWJRQ-UHFFFAOYSA-N 0.000 title claims abstract description 48
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims abstract description 40
- 108010017842 Telomerase Proteins 0.000 title claims abstract description 23
- 210000002932 cholinergic neuron Anatomy 0.000 title claims abstract description 21
- 229960003604 testosterone Drugs 0.000 title claims abstract description 20
- 230000004913 activation Effects 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 title claims abstract description 15
- 229940079593 drug Drugs 0.000 title claims abstract description 13
- 206010048259 Zinc deficiency Diseases 0.000 claims abstract description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000001850 reproductive effect Effects 0.000 claims description 5
- 230000000694 effects Effects 0.000 abstract description 9
- 210000004556 brain Anatomy 0.000 abstract description 7
- 210000000349 chromosome Anatomy 0.000 abstract description 6
- 239000002858 neurotransmitter agent Substances 0.000 abstract description 4
- 230000004075 alteration Effects 0.000 abstract description 3
- 238000010171 animal model Methods 0.000 abstract description 3
- 206010003883 azoospermia Diseases 0.000 abstract description 3
- 230000004927 fusion Effects 0.000 abstract description 2
- 230000036541 health Effects 0.000 abstract description 2
- 208000008634 oligospermia Diseases 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 abstract description 2
- 230000006798 recombination Effects 0.000 abstract description 2
- 238000005215 recombination Methods 0.000 abstract description 2
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 25
- 238000001994 activation Methods 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 9
- 239000011701 zinc Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OXVUXGFZHDKYLS-BLIWDXROSA-N Tormentic acid Chemical compound C1[C@@H](O)[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@](O)(C)[C@H]5C4=CC[C@@H]3[C@]21C OXVUXGFZHDKYLS-BLIWDXROSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 210000000918 epididymis Anatomy 0.000 description 2
- 201000010063 epididymitis Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000004459 forage Substances 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000003411 telomere Anatomy 0.000 description 2
- 108091035539 telomere Proteins 0.000 description 2
- 102000055501 telomere Human genes 0.000 description 2
- VULLSLYDWNGNKZ-UHFFFAOYSA-N 12319Tetrahydroxyurs-12-en-28-oic acid Natural products OC1C(O)C(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)C(O)(C)C5C4=CCC3C21C VULLSLYDWNGNKZ-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- OIYFAUVFZZOOFG-INIZCTEOSA-N Evoxine Natural products COc1c(OC[C@H](O)C(C)(C)O)ccc2c(OC)c3ccoc3cc12 OIYFAUVFZZOOFG-INIZCTEOSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- OXVUXGFZHDKYLS-UHFFFAOYSA-N Jacarandic acid Natural products C1C(O)C(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)C(O)(C)C5C4=CCC3C21C OXVUXGFZHDKYLS-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002186 septum of brain Anatomy 0.000 description 1
- 208000014330 spermatogenic failure Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Reproductive Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了异尖叶碱的医药新用途，其对精子减少、畸变率等具有很好的保护作用；本发明发现了异尖叶碱能起到保护男性及其子代身体健康和提高生活质量等作用；本发明发现了异尖叶碱具有改善脑内神经递质的作用，能促进脑的胆碱能神经元的数量增加；本发明发现了异尖叶碱具有增加端粒酶活性的作用，能预防和治疗染色体降解、融合、重组，从而确保遗传信息的完整性。以缺锌小鼠为动物模型，观察了异尖叶碱对缺锌小鼠的精子数量、睾酮含量，脑内胆碱能神经元、端粒酶活性的影响，提供了一种异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用。
Description
技术领域
本发明属于异尖叶碱的医药新用途技术领域，具体涉及一种异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用。
背景技术
锌是一种人体必需的微量元素，锌元素缺乏会导致多种疾病。如，缺锌容易引发不孕不育症。缺锌可以影响垂体内分泌的功能，使性激素的合成及分泌减少，血清睾酮含量改变，精子生成障碍等；一些参与脑功能的重要物质如胆碱能神经元、端粒酶等都会发生改变。
发明内容
本发明的目的在于提供一种异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用。
本发明的目的之一是提供一种异尖叶碱在制备防治缺锌所致雄性生殖障碍的药物中的应用。
所述雄性生殖障碍为精子数量少或精子畸变率高。
本发明的目的之二是提供一种异尖叶碱在制备提高睾酮含量的药物中的应用。
本发明的目的之三是提供一种异尖叶碱在制备增加胆碱能神经元数量的药物中的应用。
本发明的目的之四是提供一种异尖叶碱在制备提高端粒酶活性的药物中的应用。
本发明所属药物是指以吐曼酸为主要活性成分，与可药用载体制成的医疗上可接受的制剂，如片剂、丸剂或胶囊剂等。
本发明产生的有益效果是：本发明提供了异尖叶碱的医药新用途，其对精子减少、畸变率等具有很好的保护作用；本发明发现了异尖叶碱能起到保护男性及其子代身体健康和提高生活质量等作用；本发明发现了异尖叶碱具有改善脑内神经递质的作用，能促进脑的胆碱能神经元的数量增加；本发明发现了异尖叶碱具有增加端粒酶活性的作用，能预防和治疗染色体降解、融合、重组，从而确保遗传信息的完整性。以缺锌小鼠为动物模型，观察了异尖叶碱对缺锌小鼠的精子数量、睾酮含量，脑内胆碱能神经元、端粒酶活性的影响，提供了一种异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用。
具体实施方式
1材料与方法
1.1缺锌饲料的制备：
缺锌饲料组成成份为鸡蛋清20％，蛋氨酸0.3％，玉米淀粉66.5％，纤维素3.0％，豆油5.0％，氯化胆碱0.2％，混合维生素1.0％，混合矿物盐4.0％，使锌含量＜1mg/kg。常锌饲料在缺锌饲料的基础上添加ZnSO4·7H2O，使锌含量为50mg/kg。
异尖叶碱为成都曼思特生物科技有限公司产品。分子式:C22H28N2O4。结构式：
1.2造模和分组：
健康C57BL/6雄性小鼠8月龄随机分为4组，每组5只。随机分为对照组、缺锌组、缺锌+异尖叶碱治疗组、生理盐水组。对照组以常锌饲料喂养8周，缺锌组小鼠以缺锌饲料喂养8周，缺锌+异尖叶碱治疗组在缺锌饲料的基础上，用异尖叶碱灌胃给药(20mg/kg)，每周3次，治疗8周。载体假治疗组以缺锌饲料喂养8周，用生理盐水灌胃8周，每周3次。
1.3精子质量的检测:
在末次给药后，处死小鼠。取附睾并剪碎，加入3ml的磷酸盐缓冲液，过滤除去附睾组织碎片，用1000r/min离心收集的滤液5分钟，弃上清，将沉淀摇匀，取少量并涂在载玻片上，甲醇固定，晾干，用2％伊红染液染色10分钟，镜下观察并记录精子100个，测定畸变率，以百分率表示。
1.4血清中睾酮含量的测定：
于末次给药后30min，麻醉后摘除眼球取血，于试管中低温分离血清，用双抗体放射免疫法测定血清睾酮含量，严格按试剂盒提供的操作步骤进行。
1.5免疫组织化学染色检测胆碱能神经元的数量：
用免疫组织化学染色方法检测小鼠脑内侧隔核胆碱能神经元的数量：小鼠麻醉后4％多聚甲醛灌注固定取脑，蔗糖脱水并包埋，在冰冻切片机上作切片，片厚20μm。取内侧隔核脑区切片，加入兔抗小鼠(乙酰胆碱转移酶，ChAT)一抗，4℃冰箱孵育过夜，PBS清洗3次，加入抗兔荧光二抗，37℃孵育2h。分别计数内侧隔核视野内所有ChAT阳性细胞数。
1.6端粒酶活性检测：
小鼠处死后快速取出大脑皮层，生理盐水制成10％组织匀浆，采用ELISA进行检测端粒酶的活性。
1.7统计学处理
实验数据用均数±标准差表示，用SPSS 16.0统计软件进行统计分析，组间比较用t检验。P＜0.05为差异具有统计学意义。
2结果
2.1异尖叶碱对缺锌小鼠精子的影响
结果发现，缺锌组与对照组相比，缺锌组小鼠的精子数量显著减少，精子畸变率显著增加，差异有统计学意义(P＜0.05)；而异尖叶碱治疗组与缺锌组相比，异尖叶碱治疗组小鼠的精子数量增加，精子畸变率显著减少，差异有统计学意义(P＜0.05)(表1)。
表1异尖叶碱对精子的影响
注：*与对照组比较，P＜0.05。#与缺锌组比较，P＜0.05。
2.2异尖叶碱对缺锌小鼠血清睾酮含量变化的影响
结果显示，缺锌组与对照组相比，缺锌组小鼠的血清睾酮明显降低，差异有统计学意义(P＜0.05)；异尖叶碱治疗组与缺锌组相比，异尖叶碱治疗组小鼠的血清睾酮显著增加，差异有统计学意义(P＜0.05)(表2)。
表2异尖叶碱对血清睾酮的影响
注：*与对照组比较，P＜0.05。#与缺锌组比较，P＜0.05。
2.3异尖叶碱对小鼠内侧隔核胆碱能神经元数量的影响
结果发现，缺锌组与对照组相比，缺锌组小鼠的内侧隔核胆碱能神经元数量显著减少，差异有统计学意义(P＜0.05)；而异尖叶碱治疗组与缺锌组相比，异尖叶碱治疗组小鼠的内侧隔核胆碱能神经元数量显著增加，差异有统计学意义(P＜0.05)(表3)。
表3异尖叶碱对内侧隔核胆碱能神经元数量的影响
注：*与对照组比较，P＜0.05。#与缺锌组比较，P＜0.05。
2.4异尖叶碱对端粒酶活性的影响
结果发现，缺锌组小鼠与对照组相比，缺锌组小鼠的端粒酶活性显著降低，差异有统计学意义(P＜0.05)；而异尖叶碱治疗组与缺锌组相比，异尖叶碱治疗组小鼠的端粒酶活性显著增加，差异有统计学意义(P＜0.05)(表4)。
表4异尖叶碱对脑端粒酶活性的影响
注：*与对照组比较，P＜0.05。#与缺锌组比较，P＜0.05。
3讨论
锌是人体必需的一种微量元素，参与机体多种生理功能。本次实验通过缺锌小鼠动物模型发现:缺锌饮食可导致小鼠的精子计数减少、精子畸变率增加。血清睾酮水平大幅度降低，表明缺锌后睾丸功能受损。而异尖叶碱治疗后，可明显增加缺锌小鼠的睾酮水平，精子数量增加，精子畸变率减少。由此我们认为睾丸组织内锌缺乏可以导致生殖能力降低，而异尖叶碱能预防和治疗缺锌引起的睾酮降低、精子数量减少等。
乙酰胆碱是机体重要的神经递质，在调节学习记忆方面具有极为重要的意义。在本实验中，缺锌使小鼠脑内内侧隔核的胆碱能神经元数量减少。而给缺锌小鼠腹腔注射异尖叶碱后，胆碱能神经元的数量明显增加，这些说明，缺锌对中枢神经系统有抑制性效应，而异尖叶碱能增加脑内神经递质的作用。
端粒位于是染色体的末端，具有保护染色体的完整性和稳定性的作用，并能防止染色体被降解、融合、重组，从而确保遗传信息的完整性。端粒酶起到对端粒DNA的延伸和对断裂染色体的修复作用。本发明发现，缺锌后，小鼠脑内端粒酶活性降低；而异尖叶碱灌胃治疗后，与缺锌组比较，异尖叶碱治疗组小鼠的端粒酶活性显著增加，提示异尖叶碱有促进端粒酶活性的作用。
总之，异尖叶碱可增加缺锌引起的生殖功能改变，增加精子数量，减少精子畸形率的发生。异尖叶碱还能提高脑内内侧隔核胆碱能神经元的数，异尖叶碱能增加脑内端粒酶的活性。
Claims (5)
1.异尖叶碱在制备防治缺锌所致雄性生殖障碍的药物中的应用。
2.如权利要求1所述的应用，其特征在于：所述雄性生殖障碍为精子数量少或精子畸变率高。
3.异尖叶碱在制备提高睾酮含量的药物中的应用。
4.异尖叶碱在制备增加胆碱能神经元数量的药物中的应用。
5.异尖叶碱在制备提高端粒酶活性的药物中的应用。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2018105042441 | 2018-05-24 | ||
| CN201810504244 | 2018-05-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108815161A true CN108815161A (zh) | 2018-11-16 |
| CN108815161B CN108815161B (zh) | 2020-12-11 |
Family
ID=64149379
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811099576.2A Expired - Fee Related CN108815161B (zh) | 2018-05-24 | 2018-09-20 | 异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108815161B (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010111353A1 (en) * | 2009-03-25 | 2010-09-30 | Acadia Pharmaceuticals, Inc. | N-substituted piperidine derivatives as serotonin receptor agents |
-
2018
- 2018-09-20 CN CN201811099576.2A patent/CN108815161B/zh not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010111353A1 (en) * | 2009-03-25 | 2010-09-30 | Acadia Pharmaceuticals, Inc. | N-substituted piperidine derivatives as serotonin receptor agents |
Non-Patent Citations (1)
| Title |
|---|
| K MATSUMOTO等: "Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: Behavioural and electrophysiological studies", 《EUROPEAN JOURNAL OF PHARMACOLOGY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108815161B (zh) | 2020-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2021167341A (ja) | 治療薬のｃｎｓ送達 | |
| KR20190094124A (ko) | 분리된 미토콘드리아를 포함하는 류마티스 관절염 예방 또는 치료용 약학 조성물 | |
| Yin et al. | Inhibitory effects of palmatine on P2X7 receptor expression in trigeminal ganglion and facial pain in trigeminal neuralgia rats | |
| CN103028110A (zh) | 抗分泌因子的新用途 | |
| US20220118047A1 (en) | Method of treating glioblastoma | |
| Li et al. | Amifostine ameliorates induction of experimental autoimmune encephalomyelitis: Effect on reactive oxygen species/NLRP3 pathway | |
| Moazzam et al. | Effect of high fat diet on maternal behavior, brain‐derived neurotrophic factor and neural stem cell proliferation in mice expressing human placental lactogen during pregnancy | |
| CN108815161A (zh) | 异尖叶碱在制备提高精子性能、睾酮含量、胆碱能神经元数量和端粒酶活性的药物中的应用 | |
| KR102287877B1 (ko) | 차전자피를 포함하는 기억력 및 인지기능 증진용 조성물 | |
| CN102784160A (zh) | 连翘苷在制备改善认知功能及治疗阿尔茨海默症药物中的应用 | |
| CN109200268A (zh) | 增重化合物的组合物及其长期使用方法 | |
| KR101448155B1 (ko) | 3-메틸아데닌을 유효성분으로 함유하는 신경병증성 통증의 억제 또는 치료용 조성물 | |
| CN117045636A (zh) | 羟基红花黄色素a在治疗与血小板相关的疾病中的用途 | |
| CN107334731A (zh) | 一种牛用二丙酸咪唑苯脲注射液及其制备方法和应用 | |
| He et al. | Morinda officinalis oligosaccharides alleviate chronic unpredictable mild stress-induced depression through the BDNF/TrkB/CREB pathway and symptoms of sexual dysfunction in mice | |
| US8916607B2 (en) | Use of piperphentonamine or salts thereof in manufacture of medicaments for treating brain diseases | |
| CN105935443A (zh) | 一种治疗糖尿病性白内障的药物组合物 | |
| CN120324337B (zh) | 一种含多元微量元素和干细胞提取物的滴眼液及其制备方法和应用 | |
| Kato et al. | An ulceronecrotic foot lesion in a patient with essential thrombocythemia: successful treatment with hydroxyurea | |
| RU2325908C1 (ru) | Способ профилактики осложнений при комбинированном лечении больных раком легкого и желудка | |
| KR20200113511A (ko) | Pat4를 포함하는 만성통증 질환 예방, 개선 또는 치료용 조성물 | |
| EP4368196A1 (en) | Animal model for diseases associated with absence or reduction of social dominance, and pharmaceutical composition for preventing or treating diseases | |
| CN114306306B (zh) | 2-溴棕榈酸在制备治疗生精功能障碍相关疾病的药物中的应用 | |
| CN106389315A (zh) | 一种提高益智仁药物注射制剂稳定性的注射用药物组合物 | |
| US20250235423A1 (en) | Uses of amino acid-chelated zinc, including immune regulation and treatment of autoimmune disease |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201211 |