中药治疗出血性脑卒中的研究进展
|
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-κB(NF-κB),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。
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(PI3 K/Akt),nuclear factor kappa B(NF-κB),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.
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(PI3 K/Akt),nuclear factor kappa B(NF-κB),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.
引文
[1]Keep R F,HUA Y,XI G.Intracerebral haemorrhage:mechanisms of injury and therapeutic targets[J].Lancet Neurol,2012,11(8):720-731.
[2]Bhatia K,Hepburn M,Ziu E,et al.Modern approaches to evacuating intracerebral hemorrhage[J].Curr Cardiol Rep,2018,20(12):132.
[3]Mracsko E,Veltkamp R.Neuroinflammation after intracerebral hemorrhage[J].Front Cell Neurosci,2014,8(8):388.
[4]Obermeier B,Daneman R,Ransohoff R M.Development,maintenance and disruption of the bloodbrain barrier[J].Nat Med,2013,19(12):1584-1596.
[5]Alawieh A,Andersen M,Adkins D A L,et al.Acute complement inhibition potentiates neurorehabilitation and enhances t PA-mediated neuroprotection[J].J Neurosci,2018,38(29):6527-6545.
[6]Won S,Lee J H,Wali B,et al.Progesterone attenuates hemorrhagic transformation after delayed t PA 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.
[7]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.
[8]Cordonnier C,Demchuk A,Ziai W,et al.Intracerebral haemorrhage:current approaches to acute management[J].Lancet,2018,392(10154):1257-1268.
[9]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.
[10]CAO G,CHEN H,ZHANG Y,et al.Yi Qi Fu Mai Powder Injection ameliorates the oxygen-glucose deprivationinduced 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.
[11]CAO G,YE X,XU Y,et al.Yi Qi Fu Mai powder injection ameliorates blood-brain barrier dysfunction and brain edema after focal cerebral ischemiareperfusion injury in mice[J].Drug Des Devel Ther,2016,doi:10.2147/DDDT.S96818.
[12]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.
[13]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.
[14]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.
[15]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 JNeuroradiol,2011,32(1):41-48.
[16]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.
[17]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.
[18]CHEN Q F,LIU Y Y,PAN C S,et al.Angioedema and hemorrhage after 4.5-hour t PA(tissue-type plasminogen activator)thrombolysis ameliorated by T541 via restoring brain microvascular integrity[J].Stroke,2018,49(9):2211-2219.
[19]SHI H,ZHENG K,SU Z,et al.Sinomenine enhances microglia M2 polarization and attenuates inflammatory injury in intracerebral hemorrhage[J].JNeuroimmunol,2016,299:28-34.
[20]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.
[21]CUI H,LIU T,LI P,et al.An intersectional study of lncRNAs and mRNAs reveals the potential therapeutic targets of Buyang Huanwu Decoction in experimental intracerebral hemorrhage[J].Cell Physiol Biochem,2018,46(5):2173-2186.
[22]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.
[23]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.
[24]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.
[25]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.
[26]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.
[27]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.
[28]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.
[29]ZHAO F,DENG J,XU X,et al.Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses[J].JNeuroinflammation,2018,15(1):157.
[30]Josep P,Gerard B,Pepus D I E,et al.Highpermeability region size on perfusion CT predicts hemorrhagic transformation after intravenous thrombolysis in stroke[J].PLo S One,2017,12(11):e0188238.
[31]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.
[32]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.
[33]Nkpaa K W,Awogbindin I 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 ratiodependent pathway[J].Biol Trace Elem Res,2018,doi:10.1007/s12011-018-1587-4.
[34]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.
[35]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.
[36]ZHANG Y,YANG X,XU G,et al.Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved Caspase-3and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice[J].Biomed Pharmacother,2019,doi:10.1016/j.biopha.2018.10.161.
[37]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.
[38]CHAN P H.Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia[J].Neurochem Res,2004,29(11):1943-1949.
[39]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.
[40]TAO W,DONG Y,SU Q,et al.Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/m TORmediated BDNF/Trk B pathway[J].Behav Brain Res,2016,doi:10.1016/j.bbr.2016.04.039.
[41]ZUO W,YAN F,ZHANG B,et al.Salidroside improves brain ischemic injury by activating PI3K/Akt pathway and reduces complications induced by delayed t PAtreatment[J].Eur J Pharmacol,2018,doi:10.1016/j.ejphar.2018.04.001.
[42]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.
[43]LI Q,CHEN Y,ZHANG X,et al.Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOSpathway after subarachnoid hemorrhage in rats[J].JClin Neurosci,2016,doi:10.1016/j.jocn.2016.09.028.
[44]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/m TOR pathway[J].Neuroreport,2018,29(5):368-379.
[45]ZHOU Z Y,HUANG B,LI S,et al.Sodium tanshinone IIA sulfonate promotes endothelial integrity via regulating VE-cadherin dynamics and Rho A/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.
[46]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.
[47]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.
[48]REN J,ZHOU X,WANG J,et al.Poxue Huayu and Tianjing Busui Decoction for cerebral hemorrhage(Upregulation of neurotrophic factor expression)[J].Neural Regen Res,2013,8(22):2039-2049.
[49]HUANG Q,LAN T,LU J,et al.Di Dang Tang inhibits endoplasmic reticulum stress-mediated apoptosis induced by oxygen glucose deprivation and intracerebral hemorrhage through blockade of the GRP78-IRE1/PERKpathways[J].Front Pharmacol,2018,9(1423):1-16.
[50]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.
[2]Bhatia K,Hepburn M,Ziu E,et al.Modern approaches to evacuating intracerebral hemorrhage[J].Curr Cardiol Rep,2018,20(12):132.
[3]Mracsko E,Veltkamp R.Neuroinflammation after intracerebral hemorrhage[J].Front Cell Neurosci,2014,8(8):388.
[4]Obermeier B,Daneman R,Ransohoff R M.Development,maintenance and disruption of the bloodbrain barrier[J].Nat Med,2013,19(12):1584-1596.
[5]Alawieh A,Andersen M,Adkins D A L,et al.Acute complement inhibition potentiates neurorehabilitation and enhances t PA-mediated neuroprotection[J].J Neurosci,2018,38(29):6527-6545.
[6]Won S,Lee J H,Wali B,et al.Progesterone attenuates hemorrhagic transformation after delayed t PA 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.
[7]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.
[8]Cordonnier C,Demchuk A,Ziai W,et al.Intracerebral haemorrhage:current approaches to acute management[J].Lancet,2018,392(10154):1257-1268.
[9]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.
[10]CAO G,CHEN H,ZHANG Y,et al.Yi Qi Fu Mai Powder Injection ameliorates the oxygen-glucose deprivationinduced 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.
[11]CAO G,YE X,XU Y,et al.Yi Qi Fu Mai powder injection ameliorates blood-brain barrier dysfunction and brain edema after focal cerebral ischemiareperfusion injury in mice[J].Drug Des Devel Ther,2016,doi:10.2147/DDDT.S96818.
[12]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.
[13]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.
[14]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.
[15]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 JNeuroradiol,2011,32(1):41-48.
[16]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.
[17]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.
[18]CHEN Q F,LIU Y Y,PAN C S,et al.Angioedema and hemorrhage after 4.5-hour t PA(tissue-type plasminogen activator)thrombolysis ameliorated by T541 via restoring brain microvascular integrity[J].Stroke,2018,49(9):2211-2219.
[19]SHI H,ZHENG K,SU Z,et al.Sinomenine enhances microglia M2 polarization and attenuates inflammatory injury in intracerebral hemorrhage[J].JNeuroimmunol,2016,299:28-34.
[20]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.
[21]CUI H,LIU T,LI P,et al.An intersectional study of lncRNAs and mRNAs reveals the potential therapeutic targets of Buyang Huanwu Decoction in experimental intracerebral hemorrhage[J].Cell Physiol Biochem,2018,46(5):2173-2186.
[22]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.
[23]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.
[24]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.
[25]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.
[26]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.
[27]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.
[28]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.
[29]ZHAO F,DENG J,XU X,et al.Aquaporin-4 deletion ameliorates hypoglycemia-induced BBB permeability by inhibiting inflammatory responses[J].JNeuroinflammation,2018,15(1):157.
[30]Josep P,Gerard B,Pepus D I E,et al.Highpermeability region size on perfusion CT predicts hemorrhagic transformation after intravenous thrombolysis in stroke[J].PLo S One,2017,12(11):e0188238.
[31]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.
[32]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.
[33]Nkpaa K W,Awogbindin I 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 ratiodependent pathway[J].Biol Trace Elem Res,2018,doi:10.1007/s12011-018-1587-4.
[34]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.
[35]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.
[36]ZHANG Y,YANG X,XU G,et al.Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved Caspase-3and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice[J].Biomed Pharmacother,2019,doi:10.1016/j.biopha.2018.10.161.
[37]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.
[38]CHAN P H.Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia[J].Neurochem Res,2004,29(11):1943-1949.
[39]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.
[40]TAO W,DONG Y,SU Q,et al.Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/m TORmediated BDNF/Trk B pathway[J].Behav Brain Res,2016,doi:10.1016/j.bbr.2016.04.039.
[41]ZUO W,YAN F,ZHANG B,et al.Salidroside improves brain ischemic injury by activating PI3K/Akt pathway and reduces complications induced by delayed t PAtreatment[J].Eur J Pharmacol,2018,doi:10.1016/j.ejphar.2018.04.001.
[42]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.
[43]LI Q,CHEN Y,ZHANG X,et al.Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOSpathway after subarachnoid hemorrhage in rats[J].JClin Neurosci,2016,doi:10.1016/j.jocn.2016.09.028.
[44]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/m TOR pathway[J].Neuroreport,2018,29(5):368-379.
[45]ZHOU Z Y,HUANG B,LI S,et al.Sodium tanshinone IIA sulfonate promotes endothelial integrity via regulating VE-cadherin dynamics and Rho A/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.
[46]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.
[47]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.
[48]REN J,ZHOU X,WANG J,et al.Poxue Huayu and Tianjing Busui Decoction for cerebral hemorrhage(Upregulation of neurotrophic factor expression)[J].Neural Regen Res,2013,8(22):2039-2049.
[49]HUANG Q,LAN T,LU J,et al.Di Dang Tang inhibits endoplasmic reticulum stress-mediated apoptosis induced by oxygen glucose deprivation and intracerebral hemorrhage through blockade of the GRP78-IRE1/PERKpathways[J].Front Pharmacol,2018,9(1423):1-16.
[50]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.