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广西中医药大学 附属瑞康医院,南宁 530011
[第一作者] 王竟静,在读硕士,从事中药药学研究,E-mail:jingwj123@qq.com
*周至品,博士,主任药师,硕士生导师,从事中药药理与临床药学研究,E-mail:gxzhouzhipin@126.com
纸质出版日期:2020-05-05,
网络出版日期:2019-12-07,
收稿日期:2019-08-23,
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王竟静, 农汝楠, 覃乐, 等. 血脑屏障模型及中药对其通透性影响研究进展[J]. 中国实验方剂学杂志, 2020,26(9):225-234.
Jing-jing WANG, Ru-nan NONG, Le QIN, et al. Research Progress of Blood Brain Barrier Model and Effect of Traditional Chinese Medicine on Its Permeability[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2020,26(9):225-234.
王竟静, 农汝楠, 覃乐, 等. 血脑屏障模型及中药对其通透性影响研究进展[J]. 中国实验方剂学杂志, 2020,26(9):225-234. DOI: 10.13422/j.cnki.syfjx.20200607.
Jing-jing WANG, Ru-nan NONG, Le QIN, et al. Research Progress of Blood Brain Barrier Model and Effect of Traditional Chinese Medicine on Its Permeability[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2020,26(9):225-234. DOI: 10.13422/j.cnki.syfjx.20200607.
血脑屏障(BBB)作为脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障,能够阻止某些物质(多半是有害的)脑组织,从而保持脑组织内环境的基本稳定,但同时其阻止大多数药物进入颅内,给颅脑疾病的治疗带来困难。血脑屏障实验模型的建立是进行颅脑疾病药物治疗的一个关键技术。因此,对血脑屏障模型的建立及其通透性改变的研究,将深化对神经-血管相互作用的认识,为中枢神经系统疾病的诊疗提供重要的理论依据。中药可通过影响脑组织超氧化物歧化酶(SOD)活性、抑制髓过氧化物酶(MPO)活性及肿瘤坏死因子-
α
(TNF-
α
)含量,影响闭锁小带蛋白-1(ZO-1)的表达或上调紧密连接蛋白-5 (Claudin-5)等的表达抑制病理条件下BBB通透性,对BBB起到保护作用。中药也可通过影响细胞黏着因子-1(CAM-1),ZO-1和纤维状肌动蛋白(F-actin),P-糖蛋白(P-gp)及增加5-羟色胺(5-HT)等的表达来促进BBB通透性改变,或与其他药物共递送,增加药物透过率。本文对近年来血脑屏障实验模型建立的方法、优缺点及中药单体及有效成分、中药复方等对血脑屏障通透性作用的文献进行整理,为下一步中西医治疗颅内疾病提供重要的指导意义和方向。
Blood brain barrier (BBB)
as barrier between plasma and brain cells formed by brain capillary wall and glial cells and barrier between plasma and cerebrospinal fluid formed by choroid plexus
can prevent some brain tissues (mostly harmful substances)
so as to maintain a stable internal environment of brain tissues
while stopping most drugs from the intracranial and causeing difficulties to cerebral diseases. The establishment of experimental model of BBB is a key technique for drug treatment of craniocerebral diseases. Therefore
the establishment of the BBB model and the study of its permeability change will deepen the understanding of the neuro-vascular interaction and provide an important theoretical basis for the diagnosis and treatment of central nervous system diseases. Traditional Chinese medicine(TCM) can affect brain tissue superoxide dismutase (SOD) activity
inhibit myeloperoxidase (MPO) activity and tumor necrosis factor-
α
(TNF-
α
) content
so as to affect the expression of zonula occluden-1 (ZO-1) or up-regulate the expression of Claudin-5
inhibit BBB permeability under pathological conditions
and play a protective role in BBB. TCM can also promote the changes in BBB permeability by affecting the expressions of cell adhesion factor-1 (CAM-1)
ZO-1
filamentous actin(F-actin)
P-glycoprotein(P-gp)and 5-hydroxytryptamine (5-HT)
or increase drug permeability through co-delivery with other drugs. In this paper
the methods
advantages and disadvantages of the establishment of experimental models of the BBB in recent years
as well as the effects of TCM monomers
effective components and TCM compounds on the permeability of the BBB were summarized
so as to provide important guidance and direction for the future treatment of intracranial diseases by traditional Chinese and western medicine.
中药血脑屏障通透性研究进展
traditional Chinese medicineblood-brain barrier modelpermeabilityresearch progress
M A KAISAR, R K SAJJA, S PRASAD, et al. New experimental models of the blood-brain barrier for CNS drug discovery [J].Expert Opin Drug Discov, 2017, 12(1): 89-103.
W M PARDRIDGE. Drug Transport across the Blood-Brain Barrier [J].J Cereb Blood Flow Metab, 2012, 32(11): 1959-1972.
T FAAL, DT T PHAN, H DAVTYAN, et al. Induction of mesoderm and neural crest-derived pericytes from human pluripotent stem cells to study blood-brain barrier interactions [J].Stem Cell Rep, 2019, 12(3): 451-460.
Y YAO, Z L CHEN, E H NORRIS, et al. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity [J].Nat Commun, 2014, 5:3413.
H C HELMS, N J ABBOTT, M BUREK, et al. In vitro models of the blood-brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use [J].J Cereb Blood Flow Metab, 2016, 36(5): 862-890.
M D SWENNEY, S AYYADURAI, B V ZLOKOVIC. Pericytes of the neurovascular unit: key functions and signaling pathways [J].Nat Neurosci, 2016, 19(6): 771-783.
S GEYER, M JACOBS, N J HSU. Immunity against bacterial infection of the central nervous system: an astrocyte perspective[J].Front Mol Neurosci, 2019, 12:57
Z ZHAO, A R NELSON, C BETSHOLTZ, et al. Establishment and dysfunction of the blood-brain barrier [J].Cell, 2015, 163(5): 1064-1078.
A R CALABRIA, C WEIDENFELLER, A R JONES, et al. Puromycin-purified rat brain microvascular endothelial cell cultures exhibit improved barrier properties in response to glucocorticoid induction [J].J Neurochem, 2006, 97(4): 922-933.
N J ABBOTT, D E DOLMAN, S DRNDARSKI, et al. An improved in vitro blood-brain barrier model: rat brain endothelial cells co-cultured with astrocytes [J].Methods Mol Biol, 2012, 814:415-430.
L YANG, K K SHAN, T J ABBRUSCATO. An in vitro model of ischemic stroke [J].Methods Mol Biol, 2012, 814:451-466.
A ARMULIK, G GENOVE, M MAE, et al. Pericytes regulate the blood-brain barrier [J].Nature, 2010, 468(7323): 557-561.
查雨锋,傅晓钟,张顺,等.大鼠脑微血管内皮细胞与周细胞、星形胶质细胞共培养建立体外血脑屏障模型[J].中国药理学通报,2015, 31(5): 730-735.
D ZENKER, D BEGLEY, H BRATZKE, et al. Human blood-derived macrophages enhance barrier function of cultured primary bovine and human brain capillary endothelial cells [J].J Physiol, 2003, 551(Pt3): 1023-1032.
L CUCULLO, M HOSSAIN, V PUVENNA, et al. The role of shear stress in blood-brain barrier endothelial physiology [J].BMC Neurosci, 2011, doi: 10.1186/1471-2202-12-40http://dx.doi.org/10.1186/1471-2202-12-40.
A D VAN DER MEER, A VAN DEN BERG. Organs-on-chips: breaking the in vitro impasse [J].Integr Biol (Camb), 2012, 4(5): 461-470.
L CUCULLO, P O COURAUD, B WEKSLER, et al. Immortalized human brain endothelial cells and flow-based vascular modeling: a marriage of convenience for rational neurovascular studies [J].J Cereb Blood Flow Metab, 2008, 28(2): 312-328.
R BOOTH, H KIM. Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model [J].Ann Biomed Eng, 2014, 42(12): 2379-2391.
B PRABHAKARPANDIAN, M C SHEN, J B NICHOLS, et al. SyM-BBB: a microfluidic blood brain barrier model [J].Lab Chip, 2013, 13(6): 1093-1101.
A K ACHYUTA, A J CONWAY, R B CROUSE, et al. A modular approach to create a neurovascular unit-on-a-chip [J].Lab Chip, 2013, 13(4): 542-553.
D J ALCENDOR, FE R D BLOCK, D E CLIFFEL, et al. Neurovascular unit on a chip: implications for translational applications [J].Stem Cell Res Ther, 2013, 4(1): 18.
S P DEOSARKAR, B PRABHAKARPANDIAN, B WANG, et al. A novel dynamic neonatal blood-brain barrier on a chip [J].PLoS One, 2015, 10(11): e142725.
蒋丽莉,郑峻松,李艳,等.基于微流控芯片的体外血脑屏障模型构建[J].中国生物工程杂志,2017, 37(12): 1-7.
Y I WANG, H E ABACI, M L SHULER. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening[J].Biotechnol Bioeng, 2017,114(1):184-194.
邵新然,蔡克瑞,贾茹,等.冰片对脑缺血再灌注损伤模型大鼠炎症反应和血脑屏障通透性的影响[J].中国临床药理学杂志,2018, 34(13): 1558-1560.
S WU, N WANG, J LI, et al. Ligustilide ameliorates the permeability of the blood-brain barrier model in vitro during oxygen-glucose deprivation injury through HIF/VEGF pathway [J].J Cardiovasc Pharmacol, 2019, 73(5):316-325.
彭镜,尹飞,李玉飞,等.川芎嗪对内毒素脂多糖诱导的体外血脑屏障模型通透性增高的保护作用及其机制[J].解剖学杂志,2007,30(5): 594-596.
李玉芳,刘坤,倪月秋,等.川芎嗪对大鼠脑缺血再灌注后血脑屏障的保护作用及Claudin-5表达的影响[J].中国医科大学学报,2013, 42(6): 511-514.
何吉洪,杨海洋,龙江.丹酚酸B对缺糖缺氧/复糖复氧的体外血脑屏障模型的影响[J].重庆医学,2015, 44(33): 4611-4614.
范崇桂,邢娟.红景天苷对大鼠脑出血后血脑屏障损伤的保护作用研究[J].中国社区医师,2013, 15(10): 5-7.
张乐裕,刘晨阳,于顾然.黄芪甲苷对Aβ1-42诱导的体外血脑屏障模型损伤的影响及机制探究[J].中草药,2018, 49(17): 4099-4105.
张继州,钟志凤,胡娟,等.娑罗子提取物改善大鼠脑缺血再灌注后的神经功能评分并保护血脑屏障的作用研究[J].海峡药学,2018, 30(4): 32-34.
郭虹,史芳,王少峡,等.千叶素A对缺氧损伤下血脑屏障通透性的影响及其机制研究[J].中草药,2013, 44(16): 2278-2281.
甘文忠,张盛.当归多糖对脑梗死模型大鼠血脑屏障通透性的影响[J].中医学报,2016,3(31): 402-404.
闫安,谢云亮.当归多糖对脑缺血再灌注损伤大鼠脑组织氧化应激水平及炎症因子表达的影响[J].中国实验方剂学杂志,2018,24(2):123-127.
刘晨阳,白宽,于顾然.金丝桃苷对Aβ1-42介导的血脑屏障体外模型损伤的影响[J].中国实验方剂学杂志,2017, 23(17): 138-143.
徐玮,梁文意,郭彩娟,等.白果内酯通过Nrf2/HO-1信号通路改善氧化应激所致体外血脑屏障损伤的研究[J].广东药科大学学报,2019, 35(1): 69-75.
丁玲,胡毅,刘洁,等.知母皂苷对大鼠局灶性脑缺血/再灌注损伤的保护作用[J].中国现代应用药学,2018, 35(12): 1821-1825.
葛建彬,宋新建,陈丹丹,等.紫菜多糖对脑缺血再灌注损伤小鼠血脑屏障的保护作用[J].中国临床药理学杂志,2018, 34(19): 2291-2294.
刘晨阳,于顾然.芍药苷对纤维状Aβ1-42介导的血脑屏障体外模型损伤的影响[J].辽宁中医杂志,2018, 45(1): 163-166,226.
王一凡,杨霄鹏,曾志磊,等.姜黄素对脑缺血再灌注损伤大鼠MMP-2活性和血脑屏障通透性的影响[J].中国老年学杂志,2016, 36(2): 280-282.
赵祯,薛一雪.绿茶多酚对脑缺血大鼠血脑屏障通透性的影响[J].解剖科学进展,2016, 22(1): 60-64.
顾民华,洪文,唐传其,等.芒柄花素保护前脑缺血再灌注损伤中的血脑屏障并抑制神经炎症[J].暨南大学学报:自然科学与医学版,2015, 36(1): 34-39.
李文君,徐振田,索大琴,等.天麻素对大鼠局灶性脑缺血损伤的保护作用研究[J].中国生化药物杂志,2014, 34(5): 40-43.
张亚洲,何前松,胡斐然,等.锦鸡儿总黄酮预处理对局灶性脑缺血再灌注损伤模型大鼠血脑屏障通透性的影响及机制研究[J].中国药房,2018, 29(13): 1793-1797.
陈杰,袁捷,韩祖成,等.三七总皂苷对脑缺血-再灌注损伤大鼠脑神经的保护作用及机制[J].中国药业,2015, 24(24): 23-25.
刘仰斌,张志花,陈亚运.苦菜总黄酮对脑缺血再灌注损伤大鼠血脑屏障的保护作用[J].宜春学院学报,2015, 37(6): 21-23.
张高炼,贺启荣,梁建平,等.黄芪对创伤性脑损伤大鼠脑紧密连接相关蛋白表达及血脑屏障通透性的影响[J].广西医学,2015, 37(3): 310-312.
于淼,周喜燕,崔换新.星蒌承气汤对脑出血大鼠模型血脑屏障通透性及神经损害、神经营养的影响[J].海南医学院学报,2018, 24(14): 1387-1390.
赵金生,孟凡征,韵殷,等.“活血开窍汤”对MCAO模型大鼠血脑屏障通透性的时效性影响[J].天津中医药,2015, 32(11): 679-683.
袁有才,张效科,问莉娜,等.新葛根芩连汤对糖尿病脑病大鼠血脑屏障通透性及occludin/Claudins-5蛋白表达的影响[J].时珍国医国药,2018, 29(9): 2108-2111.
张运克,车志英,李可.补阳还五汤联合骨髓间充质干细胞对脑缺血大鼠血脑屏障通透性的影响[J].中华中医药学刊2019,37(7):1548-1553.
刘亚芳,汪宁.通窍活血汤对脑缺血再灌注小鼠血脑屏障通透性及脑内单胺类神经递质含量的影响[J].安徽医药,2015, 19(5): 842-845.
唐冰镕,李花,刘旺华,等.加味四君子汤对脑缺血大鼠脑组织Occludin,ZO-1,Claudin-1蛋白及其mRNA表达的影响[J].中国实验方剂学杂志,2019,25(15):57-63.
胡康丽,李花,刘旺华,等.四君子汤加减对脑缺血/再灌注损伤大鼠脑组织ERK1/2,Akt,Bax表达的影响[J].中国实验方剂学杂志,2018,24(13):152-158.
兰瑞,张勇,马云枝,等.小续命汤对急性脑缺血再灌注损伤BDNF,GDNF表达的影响[J].中国实验方剂学杂志,2018,24(15):149-154.
王俊杰,楼琦,汤娟娟,等.地黄饮子对脑缺血再灌注损伤大鼠保护作用及其机制[J].中国实验方剂学杂志,2019,25(4):42-48.
别晓东,李敏,虞立,等.复方红花饮对大鼠脑挫裂伤后血脑屏障通透性和SOD、MDA水平影响的实验研究[J].中国中医急症,2016, 25(11): 2036-2038,2080.
朱文锐.安宫牛黄丸对脑外伤后血脑屏障损伤及脑水肿作用机制的研究[J].中国药物经济学,2012(6):38-39.
张楠,黄鑫,戴雨霖,等.人参三七配伍对脑缺血再灌注损伤小鼠血脑屏障通透性及脑组织炎症反应的影响[J].中国老年学杂志,2017, 37(7): 1580-1583.
李敏,王斌,曹慧,等.基于AQP-4、P-gp黄芩苷、栀子苷配伍对缺血/再灌注损伤大鼠血脑屏障保护机制研究[J].中国药理学通报,2017, 33(3): 443-444.
姚洪武,王建,刘岩,等.麝香与冰片不同配比对急性脑缺血模型小鼠血脑屏障通透性的影响[J].成都中医药大学学报,2011, 34(4): 62-64,80.
王丹丹,史国娟,于顾然.补肾益精方含药血清对β-淀粉样蛋白干预血脑屏障体外模型渗透性的影响[J].江苏中医药,2015, 47(10): 72-74.
张晓杰,费洪新,刘得水,等.丹溪痛风方对阿尔茨海默病小鼠血脑屏障通透性和海马β淀粉样蛋白-(1-40)的影响及机制[J].中国实验方剂学杂志,2016, 22(22): 118-123.
李花,刘旺华,周小青,等.健脾补土法对脑缺血再灌注大鼠脑组织MMP-2的表达及血脑屏障通透性的影响[J].湖南中医杂志,2013, 29(2): 115-117.
任立军,李净,何玲,等.益气活血法对脑缺血再灌注大鼠血脑屏障通透性及t-PA/PAI的影响[J].包头医学院学报,2018, 34(4): 94-96.
T WU, A ZHANG, H LU, et al. The role and mechanism of borneol to open the blood-brain barrier [J].Integr Cancer Ther, 2018, 17(3): 806-812.
吴引萍,郭树林.冰片对血脑肿瘤屏障开放程度及紧密连接蛋白表达的影响[J].癌症进展,2016, 14(10): 986-992.
J APARICIO-BLANCO, IA ROMERO, D K MALE, et al. Cannabidiol enhances the passage of lipid nanocapsules across the blood-brain barrier both in vitro and in vivo[J].Mol Pharm, 2019, 16(5):1999-2010.
董小平,阮鸣,喻斌,等.不同剂量冰片对栀子苷在大鼠脑内浓度的影响[J].中草药,2012, 43(7): 1366-1370.
杨乐,吴军勇,胡雄彬,等.冰片对葛根素透过体外模拟血脑屏障的影响[J].中草药,2017, 48(16): 3408-3411.
汤丹丹,张焦,王计瑞,等.冰片促进葛根素和梓醇口服吸收入脑的研究[J].中国中药杂志,2016, 41(14): 2720-2726.
王刚,曾南,王建,等.合成冰片影响血脑屏障开放促槲皮素脑吸收的研究[J].中药药理与临床,2012, 28(1): 65-68.
侯天衡,李晓波,彭崇胜.冰片对积雪草苷透过大鼠血脑屏障的影响[J].中国药房,2016, 27(28): 3939-3941.
任赵燕,张卫国,杨莹,等.冰片对苯妥英钠血药及血脑浓度影响的实验研究[J].山东中医杂志,2015, 34(8): 605-617.
刁尧,刘新宁,王瓯越,等.冰片对MnTBAP透过大鼠血脑屏障的影响[J].解剖科学进展,2013, 19(5): 410-412.
黄丽平,马阮昕,冯真英,等.石菖蒲挥发油有效成分联合左旋多巴对6-羟基多巴诱导帕金森病模型大鼠血脑屏障的影响[J].时珍国医国药,2017, 28(1): 59-62.
刘萍,于绍帅,何新荣.MD-HPLC联用研究中药苏合香对西药舒必利脑药和血药浓度的影响[J].中国中药杂志,2012, 37(21): 3307-3311.
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