中药治疗出血性脑卒中的研究进展

王美娟; 潘雪薇; 张媛媛; 李芳; 寇俊萍

doi:10.13422/j.cnki.syfjx.20191740

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中药治疗出血性脑卒中的研究进展

综述 | 更新时间：2021-02-09

- 中药治疗出血性脑卒中的研究进展
- Research Progress on Amelioration of Hemorrhagic Stroke by Traditional Chinese Medicine
- 中国实验方剂学杂志 2019年25卷第17期页码：226-234
- 作者机构：
  
  中国药科大学　中药学院　江苏省中药评价与转化重点实验室，南京　 211198
- 作者简介：
  
  王美娟，在读硕士，从事中药复方作用机制的研究，E-mail：wmjzyy@qq.com
  寇俊萍，博士，教授，从事中药复方作用机制的研究，E-mail：junpingkou@163.com
- 基金信息：
  
  国家自然科学基金项目(81274004);江苏省研究生科研与实践创新计划项目(KYCX17_0668)
- DOI：10.13422/j.cnki.syfjx.20191740
  中图分类号： R2-0; R285; R722.15+ 1; R322.81
- 收稿日期：2019-04-09，
  
  网络出版日期：2019-05-17，
  
  纸质出版日期：2019-09-05
- 稿件说明：
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王美娟, 潘雪薇, 张媛媛, 等. 中药治疗出血性脑卒中的研究进展[J]. 中国实验方剂学杂志, 2019,25(17):226-234.

Mei-juan WANG, Xue-wei PAN, Yuan-yuan ZHANG, et al. Research Progress on Amelioration of Hemorrhagic Stroke by Traditional Chinese Medicine[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 226-234.
王美娟, 潘雪薇, 张媛媛, 等. 中药治疗出血性脑卒中的研究进展[J]. 中国实验方剂学杂志, 2019,25(17):226-234. DOI： 10.13422/j.cnki.syfjx.20191740.

Mei-juan WANG, Xue-wei PAN, Yuan-yuan ZHANG, et al. Research Progress on Amelioration of Hemorrhagic Stroke by Traditional Chinese Medicine[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 226-234. DOI： 10.13422/j.cnki.syfjx.20191740.

摘要

脑出血，也称出血性卒中，是指非外伤性脑实质内出血，是中老年人的常见病、多发病，具有病死率高、致残率高等特点，绝大多数存活者遗留严重的神经功能缺损症状，严重威胁人类健康和生活质量。出血性脑卒中的病理过程比较复杂，主要包括血肿的形成及扩大、颅内压升高、血脑屏障的破坏、脑水肿、神经细胞凋亡以及神经功能障碍。目前西医治疗脑出血的主要方法有抗血小板治疗、降压以及祛除血肿的外科手术等，然而通常伴有手术造成的再出血、感染、神经损伤、有效灌注压不足等风险。中医认为，瘀血阻滞、内生热毒是急性期脑出血的最基本病机。研究证实许多中药可以改善脑出血相关的血脑屏障损伤、脑水肿、神经细胞凋亡以及神经功能障碍，从而减轻脑出血损伤，其调控的主要信号转导通路包括水通道转运蛋白4(AQP4)相关分子通路，磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)分子通路，核转录因子-

B(NF-

B)，肿瘤阻抑蛋白/B-细胞白血病淋巴瘤-2-相关X蛋白/半胱氨酸蛋白酶-3(P53/Bax/Caspase-3)分子通路等。本文从目前中药对脑出血介导脑损伤的改善作用以及干预的分子通路出发，综述近十年来发表在国外期刊的相关研究进展，以期为中医药防治出血性脑卒中的临床应用和进一步新药研发提供线索和参考依据。

Abstract

Cerebral hemorrhage

also known as hemorrhagic stroke

refers to non-traumatic intracerebral hemorrhage. Cerebral hemorrhage is a common and frequently-occurring disease in middle-aged and elderly people. It has the characteristics of high mortality and high disability rate. Most survivors have serious neurological deficits

which seriously threaten human health and quality of life.The pathological process of cerebral hemorrhage is more complicated

including the formation and expansion of hematoma

elevated intracranial pressure

destruction of blood-brain barrier

brain edema

neuronal apoptosis and neurological dysfunction.At present

the main methods for treating cerebral hemorrhage by western medicine include antiplatelet therapy

blood pressure reduction and hematoma surgery. However

it is usually accompanied by the risk of rebleeding caused by surgery

infection

nerve damage and insufficient effective perfusion pressure. Chinese medicine believes that blood stasis and endogenous fever are the most basic pathogenesis of acute cerebral hemorrhage. The previous studies found that many traditional Chinese medicine(TCM) can improve blood-brain barrier damage

brain edema

neuronal apoptosis and neurological dysfunction related to cerebral hemorrhage to reduce cerebral hemorrhage injury. Main signal transduction pathways regulated by TCM to treat cerebral hemorrhageinclude Aquaporin 4(AQP4)-related

phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)

nuclear factor kappa B(NF-

suppressor protein 53/Bcl-2-associated X protein/Caspase-3(p53/Bax/Caspase-3)molecular pathways

etc.In this paper

based on the current Chinese medicine to improve the brain damage caused by cerebral hemorrhage and the molecular pathway of intervention

it reviews the research progress published in foreign journals in the past ten years

in order to provide clues and reference for the treatment of hemorrhagic stroke diseases and and the further development of new drugs.

关键词

Keywords

references

Keep R F , HUA Y , XI G . Intracerebral haemorrhage: mechanisms of injury and therapeutic targets [J]. Lancet Neurol , 2012 , 11 ( 8 ): 720 - 731 .

Bhatia K , Hepburn M , Ziu E , et al . Modern approaches to evacuating intracerebral hemorrhage [J]. Curr Cardiol Rep , 2018 , 20 ( 12 ): 132 .

Mracsko E , Veltkamp R . Neuroinflammation after intracerebral hemorrhage [J]. Front Cell Neurosci , 2014 , 8 ( 8 ): 388 .

Obermeier B , Daneman R , Ransohoff R M . Development, maintenance and disruption of the blood-brain barrier [J]. Nat Med , 2013 , 19 ( 12 ): 1584 - 1596 .

Alawieh A , Andersen M , Adkins D A L , et al . Acute complement inhibition potentiates neurorehabilitation and enhances tPA-mediated neuroprotection [J]. J Neurosci , 2018 , 38 ( 29 ): 6527 - 6545 .

Won S , Lee J H , Wali B , et al . Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF–MMP pathway [J]. J Cereb Blood Flow Metab , 2014 , 34 ( 1 ): 72 - 80 .

Salman R A S , Law Z K , Bath P M , et al . Haemostatic therapies for acute spontaneous intracerebral haemorrhage [J]. Cochrane Database Syst Rev , 2018 , doi: 10.1002/14651858.CD005951.pub4 http://doi.org/10.1002/14651858.CD005951.pub4 .

Cordonnier C , Demchuk A , Ziai W , et al . Intracerebral haemorrhage: current approaches to acute management [J]. Lancet , 2018 , 392 ( 10154 ): 1257 - 1268 .

田婷，过伟峰，李国春．急性脑出血瘀热病机临床表征研究 [J]．中医杂志， 2016 ， 57 ( 10 )： 838 - 842 ．

CAO G , CHEN H , ZHANG Y , et al . YiQiFuMai Powder Injection ameliorates the oxygen-glucose deprivation-induced brain microvascular endothelial barrier dysfunction associated with the NF-κB and ROCK1/MLC signaling pathways [J]. J Ethnopharmacol , 2016 , doi: 10.1016/j.jep.2016.02.028 http://doi.org/10.1016/j.jep.2016.02.028 .

CAO G , YE X , XU Y , et al . YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia-reperfusion injury in mice [J]. Drug Des Devel Ther , 2016 , doi: 10.2147/DDDT.S96818 http://doi.org/10.2147/DDDT.S96818 .

LU X , Chenroetling J , Regan R F . Systemic hemin therapy attenuates blood–brain barrier disruption after intracerebral hemorrhage [J]. Neurobiol Dis , 2014 , 70 ( 5 ): 245 - 251 .

ZHOU Q B , JIN Y L , JIA Q , et al . Baicalinattenuates brain edema in a rat model of intracerebral hemorrhage [J]. Inflammation , 2014 , 37 ( 1 ): 107 - 115 .

WANG Y , PENG F , XIE G , et al . Rhubarb attenuates blood-brain barrier disruption via increased zonula occludens-1 expression in a rat model of intracerebral hemorrhage [J]. Exp Ther Med , 2016 , 12 ( 1 ): 250 - 256 .

Hom J , Dankbaar J W , Soares B P , et al . Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke . [J]. Am J Neuroradiol , 2011 , 32 ( 1 ): 41 - 48 .

Lee M , Saver J L , Alger J R , et al . Blood–brain barrier permeability derangements in posterior circulation ischemic stroke: frequency and relation to hemorrhagic transformation [J]. J Neurol Sci , 2012 , 313 ( 1/2 ): 142 - 146 .

LIM , ZHOU J , JIN W , et al . Danhonginjection combined with t-PA improves thrombolytic therapy in focal embolic stroke [J]. Front Pharmacol , 2018 , 9 ( 308 ): 1 - 11 .

CHEN Q F , LIU Y Y , PAN C S , et al . Angioedema and hemorrhage after 4.5-hour tPA (tissue-type plasminogen activator) thrombolysis ameliorated by T541 via restoring brain microvascular integrity [J]. Stroke , 2018 , 49 ( 9 ): 2211 - 2219 .

SHI H , ZHENG K , SU Z , et al . Sinomenine enhances microglia M2 polarization and attenuates inflammatory injury in intracerebral hemorrhage [J]. J Neuroimmunol , 2016 , 299 : 28 - 34 .

SHAO Z , WU P , WANG X , et al . Tetramethylpyrazine protects against early brain injury and inhibits the PERK/Akt pathway in a rat model of subarachnoid hemorrhage [J]. Neurochem Res , 2018 , 43 ( 8 ): 1650 - 1659 .

CUI H , LIU T , LI P , et al . An intersectional study of lncRNAs and mRNAs reveals the potential therapeutic targets of BuyangHuanwu Decoction in experimental intracerebral hemorrhage [J]. Cell Physiol Biochem , 2018 , 46 ( 5 ): 2173 - 2186 .

CUI H J , YANG A , ZHOU H J , et al . Buyanghuanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage [J]. BMC Complement Altern Med , 2015 , 15 ( 1 ): 91 .

CHEN J C . The effects of acupuncture and traditional Chinese medicines on apoptosis of brain tissue in a rat intracerebral hemorrhage model [J]. Physiol Behav , 2015 , 151 : 421 - 425 .

PENG Y , HE P , FAN L , et al . Neuroprotectiveeffects of Magnesium Lithospermate B against subarachnoid hemorrhage in rats [J]. Am J Chin Med , 2018 , 46 ( 6 ): 1225 - 1241 .

CAI M , YU Z , ZHANG W , et al . Sheng-Di-Da-Huang Decoction inhibited inflammation expressed in microglia after intracerebral hemorrhage in rats [J]. Evid Based Complement Alternat Med , 2018 , doi: 10.1155/2018/6470534 http://doi.org/10.1155/2018/6470534 .

XU J , QIU G , HUANG J , et al . Internalization of aquaporin-4 after collagenaseinduced intracerebral hemorrhage [J]. Anat Rec (Hoboken) , 2015 , 298 ( 3 ): 554 - 561 .

YANG Y , ZHANG Y , WANG Z , et al . Attenuation of acute phase injury in rat intracranial hemorrhage by cerebrolysin that inhibits brain edema and inflammatory response [J]. Neurochem Res , 2016 , 41 ( 4 ): 748 - 757 .

YAN J H , Khatibi N H , HAN H B , et al . p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K＋ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage [J]. CNS Neurosci Ther , 2012 , 18 ( 4 ): 334 - 342 .

ZHAO F , DENG J , XU X , et al . Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses [J]. J Neuroinflammation , 2018 , 15 ( 1 ): 157 .

Josep P , Gerard B , Pepus D I E , et al . High-permeability region size on perfusion CT predicts hemorrhagic transformation after intravenous thrombolysis in stroke [J]. PLoS One , 2017 , 12 ( 11 ): e0188238 .

WANG Z , MENG C J , SHEN X M , et al . Potential contribution of hypoxia-inducible factor-1α, aquaporin-4, and matrix metalloproteinase-9 to blood-brain barrier disruption and brain edema after experimental subarachnoid hemorrhage [J]. J Mol Neurosci , 2012 , 48 ( 1 ): 273 - 280 .

Lee J J , Hsu W H , Yen T L , et al . Traditional Chinese medicine, Xue-Fu-Zhu-Yu decoction, potentiates tissue plasminogen activator against thromboembolic stroke in rats [J]. J Ethnopharmacol , 2011 , 134 ( 3 ): 824 - 830 .

Nkpaa K W , AwogbindinI O , Amadi B A , et al . Ethanol exacerbates manganese-induced neurobehavioral deficits, striatal oxidative stress, and apoptosis via regulation of p53, Caspase-3, and Bax/Bcl-2 ratio-dependent pathway [J]. Biol Trace Elem Res , 2018 , doi: 10.1007/s12011-018-1587-4 http://doi.org/10.1007/s12011-018-1587-4 .

XIE Y L , ZHANG B , JING L . MiR-125b blocks Bax/Cytochrome C/Caspase-3 apoptotic signaling pathway in rat models of cerebral ischemia-reperfusion injury by targeting p53 [J]. J Neurosurg , 2018 , 40 ( 10 ): 828 - 837 .

CHEN D , TANG J , Khatibi N H , et al . Treatment with Z-ligustilide, a component of Angelica sinensis, reduces brain injury after a subarachnoid hemorrhage in rats [J]. J Pharmacol Exp Ther , 2011 , 337 ( 3 ): 663 - 672 .

ZHANG Y , YANG X , XU G , et al . Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved Caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice [J]. Biomed Pharmacother , 2019 , doi: 10.1016/j.biopha.2018.10.161 http://doi.org/10.1016/j.biopha.2018.10.161 .

WANG S , ZHENG W , CHEN D , et al . Ginsenoside RB1 reduces neurologic damage, is anti-apoptotic, and down-regulates p53 and Bax in subarachnoid hemorrhage [J]. Curr Neurovasc Res , 2010 , 7 ( 2 ): 85 - 94 .

CHAN P H . Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia [J]. Neurochem Res , 2004 , 29 ( 11 ): 1943 - 1949 .

MA C , CHENG F , WANG X , et al . Erythropoietin pathway: a potential target for the treatment of depression [J]. Int J Mol Sci , 2016 , 17 ( 5 ): 677 .

TAO W , DONG Y , SU Q , et al . Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway [J]. Behav Brain Res , 2016 , doi: 10.1016/j.bbr.2016.04.039 http://doi.org/10.1016/j.bbr.2016.04.039 .

ZUO W , YAN F , ZHANG B , et al . Salidroside improves brain ischemic injury by activating PI3K/Akt pathway and reduces complications induced by delayed tPAtreatment [J]. Eur J Pharmacol , 2018 , doi: 10.1016/j.ejphar.2018.04.001 http://doi.org/10.1016/j.ejphar.2018.04.001 .

Nguyen H T T , Nguyen H T , Islam M Z , et al . Antagonistic effects of Gingko biloba and Sophora japonica on cerebral vasoconstriction in response to histamine, 5-hydroxytryptamine, U46619 and bradykinin [J]. Am J Chin Med , 2016 , 44 ( 8 ): 1607 - 1625 .

LI Q , CHEN Y , ZHANG X , et al . Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats [J]. J Clin Neurosci , 2016 , doi: 10.1016/j.jocn.2016.09.028 http://doi.org/10.1016/j.jocn.2016.09.028 .

GUO D , XIE J , ZHAO J , et al . Resveratrol protects early brain injury after subarachnoid hemorrhage by activating autophagy and inhibiting apoptosis mediated by the Akt/mTOR pathway [J]. Neuroreport , 2018 , 29 ( 5 ): 368 - 379 .

ZHOU Z Y , HUANG B , LI S , et al . Sodium tanshinone IIA sulfonate promotes endothelial integrity via regulating VE-cadherin dynamics and RhoA/ROCK-mediated cellular contractility and prevents atorvastatin-induced intracerebral hemorrhage in zebrafish [J]. Toxicol Appl Pharmacol , 2018 , doi: 10.1016/j.taap.2018.04.037 http://doi.org/10.1016/j.taap.2018.04.037 .

HUANG M , HU Y Y , DONG X Q , et al . The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain [J]. J Ethnopharmacol , 2012 , 143 ( 1 ): 228 - 235 .

CHEN M , LAI L , LI X , et al . Baicalein attenuates neurological deficits and preserves blood–brain barrier integrity in a rat model of intracerebral hemorrhage [J]. Neurochem Res , 2016 , 41 ( 11 ): 3095 - 3102 .

REN J , ZHOU X , WANG J , et al . PoxueHuayu and TianjingBusui Decoction for cerebral hemorrhage (Upregulation of neurotrophic factor expression) [J]. Neural Regen Res , 2013 , 8 ( 22 ): 2039 - 2049 .

HUANG Q , LAN T , LU J , et al . DiDang Tang inhibits endoplasmic reticulum stress-mediated apoptosis induced by oxygen glucose deprivation and intracerebral hemorrhage through blockade of the GRP78-IRE1/PERK pathways [J]. Front Pharmacol , 2018 , 9 ( 1423 ): 1 - 16 .

LI X , HUANG X , TANG Y , et al . Assessing the pharmacological and therapeutic efficacy of traditional chinesemedicine Liangxue Tongyu prescription for intracerebral hemorrhagic stroke in neurological disease models [J]. Front Pharmacol , 2018 , 9 ( 1169 ): 1 - 17 .

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