破血化瘀、填精补髓法对实验性脑出血大鼠内源性神经干细胞的影响
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摘要
目的：通过研究大鼠脑出血后神经干细胞的反应过程及在这一过程中相关因子的变化,探讨破血化瘀、填精补髓法对神经干细胞增殖分化的影响;并以脑源性神经营养因子(BDNF)、碱性成纤维细胞生长因子(bFGF)和内源性干细胞因子(SCF)为切入点,通过探讨该法对脑源性神经营养因子(BDNF)、碱性成纤维细胞生长因子(bFGF)和内源性干细胞因子(SCF)的调控机理,研究其对脑出血周围组织损伤修复的机制和对NSC增殖、分化的影响。据此进一步确定破血化瘀、填精补髓法的治疗作用,拓宽了现代医学理论基础,为出血性中风治疗提供一条行之有效的方法,为临床的广泛运用提供科学依据；从NSC入手研究中医药治疗出血性脑卒中,阐明脑出血后NSC增殖、分化的机制,用中医药疗法加以诱导和加强,发挥NSC的自我修复潜力,以促进出血性脑卒中神经功能恢复,重建受损的神经网络。将脑病发病病机关键学说--髓虚毒损进一步完善,并丰富脑髓理论。
方法：本研究选择Wistar大鼠,采用Bederson方法造成实验性脑出血模型,在造模后1、3、7d即症状的急性期分别取材,观察实验性脑出血大鼠血肿、水肿和神经功能缺损等整体动物行为学指标在破血化瘀、填精补髓治法的影响下的变化；实验观察实验性脑出血大鼠内源性NSC增殖分化在破血化瘀、填精补髓治法的影响下的变化；并进一步观察破血化瘀、填精补髓治法对诱导NSC增殖分化的的神经营养因子BDNF、碱性成纤维细胞bFGF、内源性干细胞因子SCP蛋白表达的影响。进一步设计实验选择观察表达相对明显的蛋白其相应受体的蛋白的表达情况及该信号转导通路的mRNA的表达情况。
结果：
(1)在给药第3天和7天分别观察对照药、实验方剂药及模型组大鼠神经功能缺损评分,与模型组大鼠比较,各组大鼠症状明显改善,神经功能缺损评分明显降低,并具有统计学意义(P<0.05或P<0.01)。
(2)在给药第三天、第七天,对照药组,实验方剂低、中,高剂量组与模型组大鼠比较脑出血面积明显降低,具有显著统计学意义(P<0.05,P<0.001,P<0.001)。
(3)在给药第三天后,对照药组、实验方剂中、高剂量组与模型组大鼠比较脑含水量明显降低,有显著性差异(P<0.05,P<0.01)。
(4)给药第三天,实验方剂中剂量组Nestin阳性细胞光密度明显增高,与模型组比有显著的统计学意义(P<0.05)。受试药高剂量组Nestin阳性细胞总而积及光密度明显增高,与模型组比较具有显著的统计学意义(P<0.05)。第七天,对照组、实验方剂低剂量组Nestin阳性细胞总面积明显增高,与模型组比较具有显著的统计学意义(P<0.05),实验方剂中、高剂量组Nestin阳性细胞总面积及光密度明显增高,与模型组比有显著的统计学意义(P<0.01,P<0.01)。
(5)给药第一天,与模型组比较,实验方剂高剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.05)。第三天,实验方剂高、低剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.05,P<0.05)。第七天,实验方剂高、中剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.01,P<0.05)。
(6)随着时间的变化,神经干细胞的分化与实验方剂药物浓度明显关联。在给药第三天,第七天,实验方剂高剂量组和中剂量组BrdU/GFAP、BrdU/NSE双标阳性细胞明显增高,与模型组比较具有显著的统计学意义(P<0.05, P<0.05, P<0.001)。
(7)对照组、实验方剂低、中、高剂量组大鼠BDNF阳性细胞数目在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第三、七天BDNF阳性细胞数目明显增加,有显著的统计学意义(P<0.05,P<0.01)。
(8)在对照组及实验方剂中剂量组大鼠bFGF阳性细胞数在术后第一、三、七天,随时间变化有显著的变化,与第一天比较,第三、七天bFGF阳性细胞数目明显增加,有显著的统计学意义(P<0.01,P<0.01)。实验方剂低、高剂量组大鼠bFGF阳性细胞数数在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第七天bFGF阳性细胞数目明显增加,具有显著的统计学意义(P<0.05)。
(9)对照组、实验方剂中、高剂量组大鼠SCF阳性细胞数目在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第七天SCF阳性细胞数目明显增加,有显著的统计学意义(P<0.05)。
(10)与模型组大鼠比较,实验方剂各组大鼠的BDNFmRNA表达量明显增加,有统计学意义。
结论：通过本实验研究,证明了无论是在改善脑出血大鼠神经功能缺损,还是在促进血肿吸收、降低脑含水量方面,应用“破血化瘀,填精补髓”法方剂都有明显的作用；成功的诱导内源性NSC增殖、分化及参与病损的修复；从蛋白水平来研究其作用机制,并证明其可能为促进脑出血灶血肿周围损伤组织中脑源性神经营养因子BDNF,碱性成纤维细胞bFGF,内源性干细胞因子SCF升高,从而促进内源性NSC增殖、分化及参与病损的修复；并从基因水平来研究其作用机制,并证明其可能为促进脑出血灶血肿周围损伤组织中SCFmRNA表达有关。
Purpose:This paper explores the effect that the method of stasis-break and enriching essence and marrow proliferate and differentiation NSCs by researching rat's reaction process of NSCs after hematencephalon and changes of correlation factor in this process; takes BDNF, BFGF, SCF as cut-in point,researches the mechanism and impact that this methord acts on repairing texture around hematencephalon part and proliferating and polarising NSCs by disscussing regulation and control mechanism for BDNF, BFGF, SCF. In view of above conclusion, confirm the therapeutical effect on the methord of stasis-break and enriching essence and marrow further, broaden its modern medical theories foundation about curing hemorrhagic stroke,provide scientific evidence for clinical wide spread application; With the view to induce NSCs'proliferation and polarization and take part in curing lesion by traditional Chinese medicine, explores a new interposing regulatory mechanism for reconstructing neurological function, provides new thought and curing means for traditional Chinese medicine deep research on this field, further deepens biological mechanism of action on Promoting neurological function damage repair by traditional Chinese medicine
Method:The research makes a model of experimental hematencephalon by Bederson on Wistar rat, draws a materials from the first, the third and the seventh day respectively during acute stage of semeiotic, observe the effect that the method of stasis-break and enriching essence and marrow changes experimental hematencephalon rats'hematoncus, oedema, neurologic impairment and other indexes of the whole ethology. Experiments observe how the method of stasis-break and enriching essence and marrow affects endogenous NSC proliferation and polarization of the experimental hematencephalon rat and further observe how the method of stasis-break and enriching essence and marrow affects BDNF, BFGF and SCF.
Result:
(1) Control drugs, experimental prescription drugs and model group rats neurological deficit scores, compared with the model group rats, the rats symptoms significantly improved neurological deficit scores were observed in the administration of3and7days reduce and statistically significant (P<0.05or P<0.01, respectively).
(2) In the administration of the third day, the seventh day, the drug-control group, experimental prescription low, medium and high dose group and the model group comparison cerebral hemorrhage area was significantly lower, with a statistically significant (P<0.05, P <0.001,P<0.001).
(3) On the third day after the administration, the drug control group, experimental recipe, the high-dose group compared with the model group rats brain water content was significantly lower, with a significant difference (P<0.05, P<0.01).
(4) Administration of the third day of Traditional middle dose group Nestin positive cells in the optical density was significantly increased compared with the model group statistically significant (P<0.05). The drug to be tested high-dose group nestin-positive cells of the total area and the optical density was significantly higher, significant statistical significance (P <0.05) compared with the model group. The seventh day, Nestin positive cells in the total area of the control group, the experimental prescription low dose group was significantly higher compared with the model group with significant statistical significance (P<0.05) and high dose groups of Traditional Nestin positive cells in a total area of light The density was significantly increased compared with the model group statistically significant (P<0.01, P <0.01).
(5) The first day of the administration, compared with model group, the experimental prescription high dose group of BrdU-positive cells was significantly higher compared with the model group statistically significant (P<0.05). The third day, the experimental prescription, BrdU-positive cells in the low dose group was significantly higher compared with the model group statistically significant (P<0.05, P<0.05). The seventh day of Traditional middle dose group of BrdU-positive cells was significantly higher compared with the model group statistically significant (P<0.01, P<0.05).
(6)The neural stem cell differentiation and experimental prescription drug concentrations were significantly associated with the change of time. In the administration of the third day, the seventh day, the the experimental prescription high dose group and middle dose group BrdU/GFAP, BrdU/NSE double-labeled positive cells was significantly higher compared with the model group has significant statistically significant (P<0.05, P<0.05, P<0.001).
(7) The control group, the experimental prescription low, medium and high dose group were BDNF positive cells after the first three or seven days, over time a significant change, with the first day than the third, seven days BDNF The number of positive cells increased significantly, there is a significant statistical significance (P<0.05, P<0.01).
(8) In the control group and the experimental prescription dose group bFGF positive cells after the first three, seven days, over time there are significant changes, compared with the first day of the third, seven-day bFGF positive cells increased significantly, there is a significant statistical significance (P<0.01, P<0.01). Of Traditional high-dose rats bFGF positive cells after surgery first, third, seven days a significant change over time, than the first day, the seventh day of bFGF positive cells increased significantly, with significant statistically significant (P<0.05).
(9) And the control group, the experimental prescription, high-dose group the number of positive cells in rat SCF after the first three or seven days, over time a significant change, with the first day of the seventh day the number of positive cells in SCF increased significantly, there is a significant statistical significance (P<0.05).
(10)Compared with the model group rats, the rats of the experimental prescription BDNFmRNA expression was significantly increased, with statistical significance.
Conclusion:According to the experiments research,proves that the method of stasis-break and enriching essence and marrow can obviously improve hematencephalon rat's neurologic impairment, promote hematoma absorption, reduce BWC;success in inducing proliferation and differentiation of endogenous NSC, participate in lesion impairment;proves that its mechanism of action may increase BDNF, BFGF and SCF around hematencephalon part from protein level, thereby, promotes proliferation and differentiation of endogenous NSC, participate in lesion impairment and proves that its mechanism of action increase SCF,mRNA and C-kitmRNA receptor around hematencephalon partfrom gene level.
方法：本研究选择Wistar大鼠,采用Bederson方法造成实验性脑出血模型,在造模后1、3、7d即症状的急性期分别取材,观察实验性脑出血大鼠血肿、水肿和神经功能缺损等整体动物行为学指标在破血化瘀、填精补髓治法的影响下的变化；实验观察实验性脑出血大鼠内源性NSC增殖分化在破血化瘀、填精补髓治法的影响下的变化；并进一步观察破血化瘀、填精补髓治法对诱导NSC增殖分化的的神经营养因子BDNF、碱性成纤维细胞bFGF、内源性干细胞因子SCP蛋白表达的影响。进一步设计实验选择观察表达相对明显的蛋白其相应受体的蛋白的表达情况及该信号转导通路的mRNA的表达情况。
结果：
(1)在给药第3天和7天分别观察对照药、实验方剂药及模型组大鼠神经功能缺损评分,与模型组大鼠比较,各组大鼠症状明显改善,神经功能缺损评分明显降低,并具有统计学意义(P<0.05或P<0.01)。
(2)在给药第三天、第七天,对照药组,实验方剂低、中,高剂量组与模型组大鼠比较脑出血面积明显降低,具有显著统计学意义(P<0.05,P<0.001,P<0.001)。
(3)在给药第三天后,对照药组、实验方剂中、高剂量组与模型组大鼠比较脑含水量明显降低,有显著性差异(P<0.05,P<0.01)。
(4)给药第三天,实验方剂中剂量组Nestin阳性细胞光密度明显增高,与模型组比有显著的统计学意义(P<0.05)。受试药高剂量组Nestin阳性细胞总而积及光密度明显增高,与模型组比较具有显著的统计学意义(P<0.05)。第七天,对照组、实验方剂低剂量组Nestin阳性细胞总面积明显增高,与模型组比较具有显著的统计学意义(P<0.05),实验方剂中、高剂量组Nestin阳性细胞总面积及光密度明显增高,与模型组比有显著的统计学意义(P<0.01,P<0.01)。
(5)给药第一天,与模型组比较,实验方剂高剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.05)。第三天,实验方剂高、低剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.05,P<0.05)。第七天,实验方剂高、中剂量组BrdU阳性细胞明显增高,与模型组比有显著的统计学意义(P<0.01,P<0.05)。
(6)随着时间的变化,神经干细胞的分化与实验方剂药物浓度明显关联。在给药第三天,第七天,实验方剂高剂量组和中剂量组BrdU/GFAP、BrdU/NSE双标阳性细胞明显增高,与模型组比较具有显著的统计学意义(P<0.05, P<0.05, P<0.001)。
(7)对照组、实验方剂低、中、高剂量组大鼠BDNF阳性细胞数目在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第三、七天BDNF阳性细胞数目明显增加,有显著的统计学意义(P<0.05,P<0.01)。
(8)在对照组及实验方剂中剂量组大鼠bFGF阳性细胞数在术后第一、三、七天,随时间变化有显著的变化,与第一天比较,第三、七天bFGF阳性细胞数目明显增加,有显著的统计学意义(P<0.01,P<0.01)。实验方剂低、高剂量组大鼠bFGF阳性细胞数数在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第七天bFGF阳性细胞数目明显增加,具有显著的统计学意义(P<0.05)。
(9)对照组、实验方剂中、高剂量组大鼠SCF阳性细胞数目在术后第一、三、七天,随时间变化有显著的变化,与第一天比,第七天SCF阳性细胞数目明显增加,有显著的统计学意义(P<0.05)。
(10)与模型组大鼠比较,实验方剂各组大鼠的BDNFmRNA表达量明显增加,有统计学意义。
结论：通过本实验研究,证明了无论是在改善脑出血大鼠神经功能缺损,还是在促进血肿吸收、降低脑含水量方面,应用“破血化瘀,填精补髓”法方剂都有明显的作用；成功的诱导内源性NSC增殖、分化及参与病损的修复；从蛋白水平来研究其作用机制,并证明其可能为促进脑出血灶血肿周围损伤组织中脑源性神经营养因子BDNF,碱性成纤维细胞bFGF,内源性干细胞因子SCF升高,从而促进内源性NSC增殖、分化及参与病损的修复；并从基因水平来研究其作用机制,并证明其可能为促进脑出血灶血肿周围损伤组织中SCFmRNA表达有关。
Purpose:This paper explores the effect that the method of stasis-break and enriching essence and marrow proliferate and differentiation NSCs by researching rat's reaction process of NSCs after hematencephalon and changes of correlation factor in this process; takes BDNF, BFGF, SCF as cut-in point,researches the mechanism and impact that this methord acts on repairing texture around hematencephalon part and proliferating and polarising NSCs by disscussing regulation and control mechanism for BDNF, BFGF, SCF. In view of above conclusion, confirm the therapeutical effect on the methord of stasis-break and enriching essence and marrow further, broaden its modern medical theories foundation about curing hemorrhagic stroke,provide scientific evidence for clinical wide spread application; With the view to induce NSCs'proliferation and polarization and take part in curing lesion by traditional Chinese medicine, explores a new interposing regulatory mechanism for reconstructing neurological function, provides new thought and curing means for traditional Chinese medicine deep research on this field, further deepens biological mechanism of action on Promoting neurological function damage repair by traditional Chinese medicine
Method:The research makes a model of experimental hematencephalon by Bederson on Wistar rat, draws a materials from the first, the third and the seventh day respectively during acute stage of semeiotic, observe the effect that the method of stasis-break and enriching essence and marrow changes experimental hematencephalon rats'hematoncus, oedema, neurologic impairment and other indexes of the whole ethology. Experiments observe how the method of stasis-break and enriching essence and marrow affects endogenous NSC proliferation and polarization of the experimental hematencephalon rat and further observe how the method of stasis-break and enriching essence and marrow affects BDNF, BFGF and SCF.
Result:
(1) Control drugs, experimental prescription drugs and model group rats neurological deficit scores, compared with the model group rats, the rats symptoms significantly improved neurological deficit scores were observed in the administration of3and7days reduce and statistically significant (P<0.05or P<0.01, respectively).
(2) In the administration of the third day, the seventh day, the drug-control group, experimental prescription low, medium and high dose group and the model group comparison cerebral hemorrhage area was significantly lower, with a statistically significant (P<0.05, P <0.001,P<0.001).
(3) On the third day after the administration, the drug control group, experimental recipe, the high-dose group compared with the model group rats brain water content was significantly lower, with a significant difference (P<0.05, P<0.01).
(4) Administration of the third day of Traditional middle dose group Nestin positive cells in the optical density was significantly increased compared with the model group statistically significant (P<0.05). The drug to be tested high-dose group nestin-positive cells of the total area and the optical density was significantly higher, significant statistical significance (P <0.05) compared with the model group. The seventh day, Nestin positive cells in the total area of the control group, the experimental prescription low dose group was significantly higher compared with the model group with significant statistical significance (P<0.05) and high dose groups of Traditional Nestin positive cells in a total area of light The density was significantly increased compared with the model group statistically significant (P<0.01, P <0.01).
(5) The first day of the administration, compared with model group, the experimental prescription high dose group of BrdU-positive cells was significantly higher compared with the model group statistically significant (P<0.05). The third day, the experimental prescription, BrdU-positive cells in the low dose group was significantly higher compared with the model group statistically significant (P<0.05, P<0.05). The seventh day of Traditional middle dose group of BrdU-positive cells was significantly higher compared with the model group statistically significant (P<0.01, P<0.05).
(6)The neural stem cell differentiation and experimental prescription drug concentrations were significantly associated with the change of time. In the administration of the third day, the seventh day, the the experimental prescription high dose group and middle dose group BrdU/GFAP, BrdU/NSE double-labeled positive cells was significantly higher compared with the model group has significant statistically significant (P<0.05, P<0.05, P<0.001).
(7) The control group, the experimental prescription low, medium and high dose group were BDNF positive cells after the first three or seven days, over time a significant change, with the first day than the third, seven days BDNF The number of positive cells increased significantly, there is a significant statistical significance (P<0.05, P<0.01).
(8) In the control group and the experimental prescription dose group bFGF positive cells after the first three, seven days, over time there are significant changes, compared with the first day of the third, seven-day bFGF positive cells increased significantly, there is a significant statistical significance (P<0.01, P<0.01). Of Traditional high-dose rats bFGF positive cells after surgery first, third, seven days a significant change over time, than the first day, the seventh day of bFGF positive cells increased significantly, with significant statistically significant (P<0.05).
(9) And the control group, the experimental prescription, high-dose group the number of positive cells in rat SCF after the first three or seven days, over time a significant change, with the first day of the seventh day the number of positive cells in SCF increased significantly, there is a significant statistical significance (P<0.05).
(10)Compared with the model group rats, the rats of the experimental prescription BDNFmRNA expression was significantly increased, with statistical significance.
Conclusion:According to the experiments research,proves that the method of stasis-break and enriching essence and marrow can obviously improve hematencephalon rat's neurologic impairment, promote hematoma absorption, reduce BWC;success in inducing proliferation and differentiation of endogenous NSC, participate in lesion impairment;proves that its mechanism of action may increase BDNF, BFGF and SCF around hematencephalon part from protein level, thereby, promotes proliferation and differentiation of endogenous NSC, participate in lesion impairment and proves that its mechanism of action increase SCF,mRNA and C-kitmRNA receptor around hematencephalon partfrom gene level.
引文
[1]Nishino H, Mida. H, Takei N, at al.Mesencephalic neural stem(progenitor) cells develop to dopaminergic neurons more strongly in dopamine-depleted striatum than in intact striatum. Exp Neurol,2000,164(1):209-214.
[2]Harrower TP, Tyers P,Hooks Y, et al. Long-term survival andintegration of porcine expanded neural precursor cell grafts in a ratmodel of Parkinson's disease. Exp Neurol,2006,197(1):56-69.
[3]Okabe S,Forsberg-Nilsson K, Spiro AC,et al. Development ofneuronal precursor cells and functional post mitotic neurons from embryonic stem cells in vitro. Mech Dev,1996,59(1):89-102.
[5]Brinton RD, Wang J M. Preclinical analyses of the therapeutic potential of allopregnanolone to promote neurogenesis in vitro and in vivo in transgenic mouse model of Alzheimer's disease.Curr Alzheimer Res,2006,3(1):11217.
[6]Freeman TB,Cicchetti F, Hauser RA, et al. Trans planted fetal striatum in Huntington's disease:phenotypic development and lack of pat hology. Proc Natl Acad Sci USA,2000,97:13877-13882.
[7]Bras ted PJ, Watts C, Robbins TW, et al. Associative plasticit y instriatial transplants. PNAS,1999,96:10524-10529.
[8]Roberts TJ, Price J, Williams SC, et al. Preservation of striatal tissue and behavioral function after neural stem cell transplantation in a rat model of Huntington's disease. Neuroscience,2006,139(4):1187-1199.
[9]Lee ST, Park J E, Lee K, et al. Noninvasive met hod of immortalized neural stem-like cell transplantation., in an experimental model of Huntington's disease. J Neurosci Met hods,2006,152(122):250-254.
[10]Riess P, Zhang C,Saat man KE,et al. Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery,2002,51(4):1043-1052.
[11]Toda H, Takahashi J, Iwakami N, et al. Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci Lett,2001,316(1) :9-12.
[12]Veizovic T,Beech J S,Stroemer P, et al. Resolution of strokeDefi-cits following contralateral grafts of conditionally immortal neuroepit helial stem cells. Stroke,2001,32:1012-1019.
[13]Watts RL, Raiser CD, Stover NP,et al. Stereotaxic intrastriatal implantation of human retinal pigment epit helial(hRPE)cells at tached to gelatin microcarriers:a potential new cell t herapy for Parkinson's disease.J Neural Transm Suppl,2003, (65):215-227.
[14]Jeong SW,Chu K, J ung KH, et al. Human neural stem cell trans-plantation promotes functional recovery in rats with experimental intracerebral hemorrhage . Stroke,2003,34(9):2258-2263.
[15]Yagita Y, Kitagawa K, Ohtsuki T, et al. Neurogenesis by progenitorcells in the ischemic adult rat hippocampus[J]. Stroke,2001; 32(8):1890-1896.
[16]Jiang W, Gu W, Brannstrom T, et al. Cortical neurogenesis in adultrats after transient middle cerebral artery occlusion[J]. Stroke,2001; 32(5):1201-1207.
[17]Leker RR,Soldner F, Velasco I, et al. Long-lasting regeneration after ischemia in the cerebral cortex[J]. Stroke,2007; 38(1):153-161.
[18]Chen Y,Sun FY.Age-related decrease of striatal neurogenesis isassociated with apoptosis of neural precursors and newborn neurons in ratbrain after ischemia[J]. Brain Res,2007; 29(1166):9-19.
[19]张均田,刘云,屈志炜,等.人参皂甙Rb1和Rg1对小鼠中枢神经递质受体和脑内蛋白质合成的影响.药学学报,1988,23(1)：12-16.
[20]Liu M, Zhang J T. Effects of ginsenoside Rgl on c-fos gene expression and cAMP levels in rat hippcampus. Acta Pharmacol Sin,1996,17(2):171-174.
[21]申丽红,张均田.人参皂苷Rg1对脑缺血沙土鼠神经干细胞存活率和学习记忆能力的影响.中南药学,2004,2(1)：6-9.
[22]张均田.人参皂苷Rgl的促智作用机制对神经可塑性和神经发生的影响.药学学报,2005,40(5)：385-388.
[23]单德红,柴纪严,王德山,等.定志小丸对抑郁模型大鼠齿状回神经干细胞和学 习记忆能力的影响.中医药学刊,2005,23(8)：1426-1427.
[24]柴纪严,单德红,王德山.定志小丸对抑郁模型大鼠海马神经干细胞Nestin表达的影响.中国中医药信息杂志,2005,12(4)：29-30.
[25]陈东风,杜少辉,李伊为,等.龟板对局灶性脑缺血后神经干细胞的作用[J].广州中医药大学学报,2001；18(4)：328-331.
[26]廖维靖,范明,杨运煌,等.当归注射液对脑缺血/再灌注神经元代谢物的影响[J].中国应用生理学杂志,2003；19(3)：209-212.
[27]张光毅,杜俊蓉,旷喜,等.当归内酯治疗局灶性脑缺血的作用机制[J].华西药学杂志,2006；21(2)：114-117.
[28]刘柏炎,蔡光先.补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响[J].中国药物与临床2005；5(3)：171-173。
[29]孙晋浩,杨琳,高英茂,等.补阳还五汤对神经干细胞生长分化的影响[J].山东大学学报(医学版)2002；10(40)：406-408
[30]高唱,王景周.左归丸对体外培养新生大鼠海马神经干细胞增殖分化的影响[J].中国医药学报,2004；19(11)：691-693.
[31]缪兵,高建新,刘星霞,等.银杏内酯B对神经细胞活性影响的实验研究.山东医药,2004,44(20)：16-18.
[32]黄镇,金国华,张新化,等.银杏内酯B对成年大鼠神经干细胞向神经元分化的促进作用.解剖学报,2003,34(4)：367-371.
[33]丁英,曾园山,张伟,等.不同浓度的银杏内酯B对培养的神经干细胞分化的影响.解剖学报,2004,35(5)：484-488.
[34]张密霞,李越,杜嵘,张艳军黄芩苷对体外培养神经干细胞分化的影响[J].天津中医药大学学报,2007；26(4)：199-201,
[35]邹凡,杨万同,田峻,等.当归注射液对全脑缺血后神经再塑影响的实验研究[J].武汉大学学报(医学版),2004；25(1)：38-41.
[36]刘建军,姚忠祥,秦茂林,等.陈建芳单味黄芪红花丹参注射液对神经干细胞分化影响的初步研究[J].第三军医大学学报,2006；28(14)：1470-1472
[37]丁英,曾园山,张伟,等.不同浓度的银杏内酯B对培养的神经干细胞分化的影响[J].解剖学报,2004；35(5)：484-488
[38]Nakashima K, Takizawa T, Ochiai W, et al.BMP2 mediated all teration in t he developmental pathway of fetal mouse brain cells fromneurogenesis to astrocytogenesis[J].Proc Natl Acad Sci USA,2001; 98:5868-5873.
[39]Ying QL, Nichols J,Chambers I.BMP induction of Id proteinssuppresses differentiation and sustains embryonic stem cell selfrenewal incollaboration with STAT3[J]. Cell,2003:115,281-292.
[40]司银楚,成龙,洪庆涛,等.三七总皂苷促进离体胎鼠皮层神经干细胞增殖、分化的实验研究.中国体视学与图像分析,2004,9(2)：78-83.
[41]程龙,朱培纯,司银楚,等.三七总皂苷对去大脑皮层血管后成年大鼠前脑侧脑室室管膜下层Nestin和bFGF表达的作用.北京中医药大学学报,2003,26(3)：18-20.
[42]赵红念,胡晓松,周东,等.三七三醇皂苷对局灶性脑缺血再灌注大鼠脑组织Nestin表达的影响.华西医学,2005,20(2)：297-299.
[43]余鸿,刘敦玉,吴雨岭,等.当归对缺氧鼠胚模型神经干细胞增殖的影响[J].中国现代医学杂志,2005；21(15)：3226-3228.
[44]崔桂云,沈霞,张璐,等.丹参神经保护作用机制的研究[J].徐州医学院学报,2002；22(6)：492-494
[45]高中洪,黄开勋,徐辉碧.黄芩黄酮对H202导致的神经细胞损伤的保护作用[J].中国药理学通报,2000;16(5)：589-590
[46]杨娟,陈付学,梁光义.刺梨多糖对神经干细胞谷氨酸损伤的保护作用.营养学报,2005,27(4)：339-341.
[47]刘柏炎,黎杏群,张化先,等.脑溢安颗粒对实验性大鼠脑出血后神经干细胞增殖的影响.中国临床康复,2003,7(25)：3428-3429.
[48]武衡,黎杏群,唐涛,等.脑溢安对大鼠海马神经干细胞分化的影响.中国临床康复,2004,8(28)：6148-6149.
[49]罗杰坤,黎杏群,刘柏炎,等.脑溢安对大鼠缺氧神经干细胞保护作用.中国临床康复,2004,8(22)：4534-4535.
[50]肖岚,黎杏群,刘柏炎,等.脑溢安对新生大鼠海马神经干细胞缺氧损伤及p38MAPK活性的影响.中国现代医学杂志,2004,14(16)：67-74.
[51]刘柏炎,蔡光先.补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响.中国药物与临床,2005,5(3)：171-173.
[52]蔡光先,刘柏炎.补阳还五汤对体外低糖低氧损伤海马神经干细胞增殖的影响. 湖南中医学院学报,2005,25(2)：1-3.
[53]刘柏炎,蔡光先,林琳,等.补阳还五汤对大鼠局灶性脑缺血后神经干细胞影响的初步研究.中国临床康复,2004,8(22)：4532-4533.
[54]高唱,王景周.左归丸对体外培养新生大鼠海马神经干细胞增殖分化的影响.中国医药学报,2004,19(11)：691-693.
[55]杨萍,王继明,应大君,等.中药制剂—肌萎灵注射液对神经干细胞的促分化作用.神经解剖学杂志,2005,21(2)：171-174.
[56]卢昌均,陆兵勋,王立新,等.缺血后再灌注损伤大鼠脑内β2微管蛋白的变化及通心络对其影响.中国急救医学,2006,26(1)：44-45.
[57]刘倩.脑出血的中西医结合研究进展(综述)[J].中国中西医结合急救杂志,2008,(15)6：381-384.
[58]杨宏勇.脑出血急性期阳闭证中医论治的思路及方法探析[J].中国中医急症,2009,18(4)：564-565.
[59]戴高中.陈汝兴.顾明昌等.大黄廑虫丸对大鼠脑出血模型神经损伤积分值和脑组织凝血酶受体mRNA表达的影响[J].辽宁中医杂志,2007,34(6)：838-841.
[60]戴高中.陈汝兴.顾明昌等.大黄麈虫丸对大鼠脑出血模型脑组织IL-1BmRNA、 NO2mRNA表达的影响[J].四川中医,2008,26(2)：18-20.
[61]张小萍.吴颢昕.刘韶华等.抵当口服液对大鼠脑出血模型C-fos蛋白表达及脑水肿指数的影响[J].中国中医急症,2007,16(5)：579-580.
[62]罗杰坤.唐涛.黎杏群等.补阳还五汤对脑出血大鼠脑内Caspase-3活化的影响[J].湖南中医学院学报,2006,26(3)：12-141.
[63]王玲.唐涛.罗杰坤等.补阳还五汤对脑出血大鼠脑内MMP2表达的影响[J].中国老年学杂志,2007,27(7)：1257-12601.
[64]高志荣.凉血化瘀法对大鼠脑出血的实验研究[J].中国中医急症,2006,15(10)：1131-1132.
[65]秦峰.王长松.晋光荣等.犀角地黄汤对大鼠脑出血后脑水肿及行为学影响的研究[J].中国中医急症,2008,17(6)：801-803.
[66]范录平.叶华.郭蕾等.卒中散对脑出血大鼠抓握能力的改善及血清S100B水平的影响[J].实用中西医结合临床,2007,7(2)：9-10.
[67]赵清超.胡久略.活血通窍贴片经皮给药对兔急性脑出血血液流变学及超氧化 物歧化酶、丙二醛的影响[J].中国临床药理学与治疗学,2008,13(7)：772-775.
[68]刘淑霞.聂伟.杜婴等.黄竹清脑口服液对急性脑出血大鼠血清中CRP及脑组织中MDA GSH-PX的影响[J].辽宁中医杂志,2008,35(12)：1936-1937.
[69]刘淑霞.白雅.任惠锋等.黄竹清脑颗粒对痰热腑实证脑出血急性期大鼠血清MDA及血浆TNF的影响[J].江西中医学院学报,2009,21(2)：62-64.
[70]王长松.晋光荣.张斌霞等.下瘀清痰汤对脑出血后脑水肿影响的实验研究[J].辽宁中医学院学报,2006,8(3)：119-120.
[71]侯俊良.梁清华.包太成等.大承气汤对脑出血大鼠神经元线粒体内细胞色素C释放的影响[J].实用预防医学,2006,13(3)：495-498.
[72]张国平.刘华.别晓东等.通腑活血汤对脑出血大鼠脑组织保护作用的病理实验研究[J].广东医学,2006,8：1152-1153.
[73]杨琴芳.许毅.秦峰等.桃核承气汤对大鼠脑出血急性期Bcl-2、Bax蛋白表达的影响[J].南京中医药大学学报,2009,25(4)：281-282.
[74]陆红.王桂敏.逐淤化痰汤对脑出血大鼠脑含水量及SOD活性的影响[J].辽医学院学报,2009,30(1)17-19.
[75]杨文清.任玉录.郭克锋等.安宫牛黄丸对急性脑出血大鼠脑组织中一氧化氮合酶及单胺类神经递质的影响[J].中国中医急症,2009,18(1)：83-84.
[76]付宪文.孙异临.党国义等.安宫牛黄丸对脑出血大鼠脑组织超微结构的影响[J].河北中医药学报,2008,23(1)：39-41.
[77]李鹏英.鲁艺.刘敏等.新清开灵注射液对大鼠脑出血后脑组织SOD、脑含水量的影响[J].山东中医杂志,2007,26(2)：116-117.
[78]周庆博.李鲁扬.贾青等.清热解毒法对脑出血大鼠的神经保护作用[J].山东大学学报(医学版),2007,45(9)：947-950.
[79]杨仲义.史载祥.方芳等.羚黄汤对实验性大鼠脑出血损伤的保护作用[J].中国中医急症,2007,16(4)：451-452.
[80]杜宝新.郑国庆.卢明等.脑脉Ⅱ号胶囊抑制脑出血后脑水肿的机理研究[J].广州中医药大学学报,2007,24(4)：297-399.
[81]何纲.黄培新.刘茂才等.脑脉Ⅱ号口服液对高血压脑出血大鼠血肿周围组织半胱氨酸天冬氨酸特异性蛋白酶-3活性和细胞凋亡的影响[J].实用医学杂志,2009,25(10)：1573-1575.
[82]陶双友.刘茂才.卢明等.脑脉Ⅱ号胶囊对脑出血所致脑心综合征大鼠心电图的影响[J].时珍国医国药,200617(3)：323-324.
[83]熊新贵.梁清华.包太成.不同中医治法对实验性脑出血大鼠Caspase-3表达的影响[J].实用预防医学,2007,14(1)：13-15.
[84]萧梅芳.梁清华.谭勇等.不同中医治法对脑出血大鼠神经元损伤及海马线粒体膜电位的影响[J].实用预防医学,2007,14(5)：1347-1349.
[85]张雨星.梁清华.谭勇等.不同中医治法对脑出血大鼠海马线粒体DNA含量的影响[J].湖南中医药大学学报,2007,27(5)：32-35.
[86]齐勇.唐涛.罗杰坤等.益气活血法对脑出血大鼠脑内TSP-1、TSP-2及其受体CD36表达的影响[J].中国老年学杂志,2007,27(10)：913-916.
[87]杨继文.王威.袁曙光等.黄芪合丹参注射液对急性脑出血大鼠神经细胞凋亡表达的影响[J].中华中医药杂志(原中国医药学报),200722(10)：720-722.
[88]聂亚雄.霍瑞民.赵强等.三七总皂苷分期治疗对脑出血大鼠微管相关蛋白-2及神经生长相关蛋白表达的影响[J].中西医结合心脑血管病杂志,2009,7(5)：547-549.
[89]霍瑞民.聂亚雄.姜波涛等.三七总皂苷对大鼠脑出血后肢体功能和MAP-2及GAP-43表达水平的影响[J].中西医结合心脑血管病杂志,2008,6(2)：168-170.
[90]聂亚雄.尹剑.朱文龙等.三七总皂苷注射液对脑出血大鼠颅内血肿及脑水肿的影响[J].湖南中医药大学学报,200929(3)：37-39.
[91]郭志松.邵换璋等.三七总皂甙对脑出血大鼠的神经保护作用[J].中国实用神经疾病杂志,2009,12(11)：42-44.
[92]周秀丽.曾光伟.李士坤等.B-七叶皂甙钠对脑出血大鼠的神经保护作用[J].中国实用神经疾病杂志,2008,11(4)：27-29.
[93]罗琳.雷久士.亚低温合七叶皂苷钠对大鼠脑出血后血肿周围Bax、Bcl-2表达的影响[J].湖南中医药大学学报,2007,27(2)：50-53.
[94]周天梅.黄晓明.韦志盖等.川芎嗪注射液治疗急性期脑出血大鼠的时间窗研究[J].中国中医急症,2009,18(1)：81-82.
[95]吴瑛.任安乐.大鼠脑出血急性期给予水蛭素后血肿周围组织胶质纤维酸性蛋白的表达[J].兰州大学学报(医学版),2009,35(1)：1-4.
[96]杨文海.宁显忠.王媛媛等.核转录因子KB在大鼠脑出血后血肿周围组织中的表达及水蛭素的保护作用[J].中西医结合心脑血管病杂志,2006,(12)：1436-1437.
[97]杨奎.闵志强.石娅萍等.栀子总环烯醚萜苷对脑出血大鼠炎症反应与神经元凋亡的影响[J].中药新药与临床药理,2009,20(1)：8-10.
[98]周乾坤.余嗣明.刘平等.黄芩苷对脑出血大鼠脑内氨基酸递质含量的影响.[J].中国中医药信息杂志,200916(4)：35-37.
[99]刘平.隗义双.周乾坤等.黄芩苷对实验性脑出血大鼠脑损伤的保护作用[J].中国中医药信息杂志,2008,15(4)：34-35.
[100]黄良国.王东.葛正龙等.刺五加对大鼠脑出血病理变化及13-EP的影响[J].中国老年学杂志,2006,26(9)：1232-1234.
[101]殷利春.杜抗根.何民等.葛根素对实验性脑出血大鼠偏瘫状态和脑组织NO含量的影响[J].中国中医药科技,2007,14(3)：173-174.
[102]张海宇.马全瑞.张莲香等.黄芪注射液对大鼠脑出血灶周围神经元超微结构的影响[J].解剖学杂志,2009,32(3)：3308-3311.
[103]许东.胡治平.秦毅等.黄芪注射液对脑出血大鼠细胞凋亡影响的研究[J].临床神经病学杂志,2008,21(1)：37-40.
[104]于君.周庆博.毕建忠等.蚤休和半边莲对大鼠脑出血后血浆细胞间黏附分子-1肿瘤坏死因子-OL的影响[J].中医药学刊,2006,24(10)：1910-1912.
[105]郑国庆.王艳.黄培新等.脑血康对急性脑出血大鼠脑组织超微结构的影响[J].中医药学刊,2006,24(5)：835-838.
[106]赵佳辉.针刺对脑出血大鼠兴奋性氨基酸含量影响的研究[J].新医学导刊,2008,7(2)：7-9.
[107]姜桂关.针刺对脑出血模型大鼠急性期血肿周围脑组织IL-113及IL-6的影响[J].广东医学,2009,30(7)：1045-1047.
[108]李奎生.论活血化瘀法在中风治疗中的地位[J].现代中西医结合杂志,2004,13(13)：1082-1083.
[109]郑国庆.出血中风急性期的治则治法阐发[J].中国医药导报,2006,17：256.
[110]张宪忠,孙宝红.急性脑卒中超早期中西医结合抢救治疗的思考[J].中国中西医结合急救杂志,1998,5(2)：49-51.
[111]刘泰.对急性脑出血脑水肿期中医病机的探讨[J].中华实用中西医志,2001,14(22)：2179.
[112]姜春华.活血化瘀研究新编[M].上海：上海医科大学出版社,1990：139.
[113]杨万章.逐瘀化痰汤对脑出血患者颅内血肿及血液流变学的影响[J].中医杂志,1996,37(1])：670.
[114]高慧娟,黄永勤,李新毅.影响急性脑出血患者血液流变学的因素分析[J].临床医学,2006,26(1)：3-5.
[115]姜兆顺.2型糖尿病血瘀证患者血小板CD62P、CD63测定意义探讨[J].中国中西医结合杂志,1999,19(9)：527.
[116]石志芸.血瘀证患者血小板α-颗粒膜蛋白、内皮素测定[J].中医杂志,1996,37(4)：239.
[117]唐宇平,蔡定芳,刘军,等.大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究[J].中国中西医结合杂志,2006,26(2)：152-156.
[118]刘泰.传统方剂五苓散加减后2种复方制剂对细胞毒性脑水肿的作用[J].中国临床康复,2006,10(11)：53-55.
[119]刘泰.传统方剂五苓散加减后的2种复方制剂对血脑屏障保护作用比较[J].中国临床康复,2006,10(15)：168-170.
[120]张永全,刘泰,陆晖,等.健神利水Ⅰ号对脑出血急性期血液流变性及超氧化物歧化酶的影响[J].中国中西医结合急救杂志,2002,9(5)：273-275.
[121]刘泰,甘照儒,陆晖,等.健神利水Ⅰ号治疗脑出血急性期脑水肿60例临床研究[J].中医杂志,2003,44(2)：103.
[122]张永全,刘泰,陆晖,等.健神利水Ⅰ号对脑出血急性期脑水肿的临床疗效[J].广西中医药,2002,25(5)：8.
[123]顾宁,王长松,周仲瑛.凉血通瘀注射液对急性脑出血患者近期疗效的影响[J].新中医,2007,39(1)：40-41.
[124]高树良,王晋朝,陈玉芹.利水逐瘀法治疗高血压性脑出血颅内压增高临床研究[J].河北中医,2002,24(4)：243-245.
[125]户文娟,杨际清.脑出血继续出血68例临床分析[J].中西医结合心脑血管病杂志,2004,2(1)：56-57.
[126]李铁山,韩仲岩.脑出血继续出血及其影响因素[J].国外医学：脑血管疾病分册,1999,7(2)：96.
[127]杨万章.出血性中风活血化癖法应用时间窗探讨[J].中国医药学报,2002,17(12)：743-745.
[128]常诚.脑出血活血化瘀治疗的影响因素[J].河北中医杂志,2003,25(3)：192-193.
[129]杨仲义,史载祥.活血化瘀法治疗高血压急性脑出血探讨[J].中国中医药信息杂志,2007,14(5)：89-90.
[130]赵耀东,李军.活血化瘀与脑出血急性期[J].甘肃中医学院学报,2002,19(4)：8.
[131]严容,张钟爱.活血化瘀法在出血性中风急性期的运用及常见问题探讨[J].江西中医学院学报,2006,18(4)：11.
[132]刘清泉,安海燕,郭建文.分层扭转法与脑出血重症[J].中国医药学报,1999,14(2)：54.
[133]朱东胜,徐敏华,卫洪昌,等.中风系列制剂治疗急性脑出血的临床与试验研究[J].中国中西医结合急救杂志,2000,7(3)：133-136.
[134]黄坚红,陈秀慧,刘健红.分期选用活血化瘀药治疗高血压性脑出血32例疗效观察[J].新中医杂志,2005,37(11)：30-31.
[135]杨继文,袁曙光,多慧玲.补阳还五汤加减治疗中小量脑出血急性期30例临床观察[J].河北中医杂志,2004,26(11)：841-842.
[136]张爱华.黄芪在脑出血中应用50例疗效观察[J].中国误诊学杂志,2002,2(9)：1351.
[2]Harrower TP, Tyers P,Hooks Y, et al. Long-term survival andintegration of porcine expanded neural precursor cell grafts in a ratmodel of Parkinson's disease. Exp Neurol,2006,197(1):56-69.
[3]Okabe S,Forsberg-Nilsson K, Spiro AC,et al. Development ofneuronal precursor cells and functional post mitotic neurons from embryonic stem cells in vitro. Mech Dev,1996,59(1):89-102.
[5]Brinton RD, Wang J M. Preclinical analyses of the therapeutic potential of allopregnanolone to promote neurogenesis in vitro and in vivo in transgenic mouse model of Alzheimer's disease.Curr Alzheimer Res,2006,3(1):11217.
[6]Freeman TB,Cicchetti F, Hauser RA, et al. Trans planted fetal striatum in Huntington's disease:phenotypic development and lack of pat hology. Proc Natl Acad Sci USA,2000,97:13877-13882.
[7]Bras ted PJ, Watts C, Robbins TW, et al. Associative plasticit y instriatial transplants. PNAS,1999,96:10524-10529.
[8]Roberts TJ, Price J, Williams SC, et al. Preservation of striatal tissue and behavioral function after neural stem cell transplantation in a rat model of Huntington's disease. Neuroscience,2006,139(4):1187-1199.
[9]Lee ST, Park J E, Lee K, et al. Noninvasive met hod of immortalized neural stem-like cell transplantation., in an experimental model of Huntington's disease. J Neurosci Met hods,2006,152(122):250-254.
[10]Riess P, Zhang C,Saat man KE,et al. Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery,2002,51(4):1043-1052.
[11]Toda H, Takahashi J, Iwakami N, et al. Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci Lett,2001,316(1) :9-12.
[12]Veizovic T,Beech J S,Stroemer P, et al. Resolution of strokeDefi-cits following contralateral grafts of conditionally immortal neuroepit helial stem cells. Stroke,2001,32:1012-1019.
[13]Watts RL, Raiser CD, Stover NP,et al. Stereotaxic intrastriatal implantation of human retinal pigment epit helial(hRPE)cells at tached to gelatin microcarriers:a potential new cell t herapy for Parkinson's disease.J Neural Transm Suppl,2003, (65):215-227.
[14]Jeong SW,Chu K, J ung KH, et al. Human neural stem cell trans-plantation promotes functional recovery in rats with experimental intracerebral hemorrhage . Stroke,2003,34(9):2258-2263.
[15]Yagita Y, Kitagawa K, Ohtsuki T, et al. Neurogenesis by progenitorcells in the ischemic adult rat hippocampus[J]. Stroke,2001; 32(8):1890-1896.
[16]Jiang W, Gu W, Brannstrom T, et al. Cortical neurogenesis in adultrats after transient middle cerebral artery occlusion[J]. Stroke,2001; 32(5):1201-1207.
[17]Leker RR,Soldner F, Velasco I, et al. Long-lasting regeneration after ischemia in the cerebral cortex[J]. Stroke,2007; 38(1):153-161.
[18]Chen Y,Sun FY.Age-related decrease of striatal neurogenesis isassociated with apoptosis of neural precursors and newborn neurons in ratbrain after ischemia[J]. Brain Res,2007; 29(1166):9-19.
[19]张均田,刘云,屈志炜,等.人参皂甙Rb1和Rg1对小鼠中枢神经递质受体和脑内蛋白质合成的影响.药学学报,1988,23(1)：12-16.
[20]Liu M, Zhang J T. Effects of ginsenoside Rgl on c-fos gene expression and cAMP levels in rat hippcampus. Acta Pharmacol Sin,1996,17(2):171-174.
[21]申丽红,张均田.人参皂苷Rg1对脑缺血沙土鼠神经干细胞存活率和学习记忆能力的影响.中南药学,2004,2(1)：6-9.
[22]张均田.人参皂苷Rgl的促智作用机制对神经可塑性和神经发生的影响.药学学报,2005,40(5)：385-388.
[23]单德红,柴纪严,王德山,等.定志小丸对抑郁模型大鼠齿状回神经干细胞和学 习记忆能力的影响.中医药学刊,2005,23(8)：1426-1427.
[24]柴纪严,单德红,王德山.定志小丸对抑郁模型大鼠海马神经干细胞Nestin表达的影响.中国中医药信息杂志,2005,12(4)：29-30.
[25]陈东风,杜少辉,李伊为,等.龟板对局灶性脑缺血后神经干细胞的作用[J].广州中医药大学学报,2001；18(4)：328-331.
[26]廖维靖,范明,杨运煌,等.当归注射液对脑缺血/再灌注神经元代谢物的影响[J].中国应用生理学杂志,2003；19(3)：209-212.
[27]张光毅,杜俊蓉,旷喜,等.当归内酯治疗局灶性脑缺血的作用机制[J].华西药学杂志,2006；21(2)：114-117.
[28]刘柏炎,蔡光先.补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响[J].中国药物与临床2005；5(3)：171-173。
[29]孙晋浩,杨琳,高英茂,等.补阳还五汤对神经干细胞生长分化的影响[J].山东大学学报(医学版)2002；10(40)：406-408
[30]高唱,王景周.左归丸对体外培养新生大鼠海马神经干细胞增殖分化的影响[J].中国医药学报,2004；19(11)：691-693.
[31]缪兵,高建新,刘星霞,等.银杏内酯B对神经细胞活性影响的实验研究.山东医药,2004,44(20)：16-18.
[32]黄镇,金国华,张新化,等.银杏内酯B对成年大鼠神经干细胞向神经元分化的促进作用.解剖学报,2003,34(4)：367-371.
[33]丁英,曾园山,张伟,等.不同浓度的银杏内酯B对培养的神经干细胞分化的影响.解剖学报,2004,35(5)：484-488.
[34]张密霞,李越,杜嵘,张艳军黄芩苷对体外培养神经干细胞分化的影响[J].天津中医药大学学报,2007；26(4)：199-201,
[35]邹凡,杨万同,田峻,等.当归注射液对全脑缺血后神经再塑影响的实验研究[J].武汉大学学报(医学版),2004；25(1)：38-41.
[36]刘建军,姚忠祥,秦茂林,等.陈建芳单味黄芪红花丹参注射液对神经干细胞分化影响的初步研究[J].第三军医大学学报,2006；28(14)：1470-1472
[37]丁英,曾园山,张伟,等.不同浓度的银杏内酯B对培养的神经干细胞分化的影响[J].解剖学报,2004；35(5)：484-488
[38]Nakashima K, Takizawa T, Ochiai W, et al.BMP2 mediated all teration in t he developmental pathway of fetal mouse brain cells fromneurogenesis to astrocytogenesis[J].Proc Natl Acad Sci USA,2001; 98:5868-5873.
[39]Ying QL, Nichols J,Chambers I.BMP induction of Id proteinssuppresses differentiation and sustains embryonic stem cell selfrenewal incollaboration with STAT3[J]. Cell,2003:115,281-292.
[40]司银楚,成龙,洪庆涛,等.三七总皂苷促进离体胎鼠皮层神经干细胞增殖、分化的实验研究.中国体视学与图像分析,2004,9(2)：78-83.
[41]程龙,朱培纯,司银楚,等.三七总皂苷对去大脑皮层血管后成年大鼠前脑侧脑室室管膜下层Nestin和bFGF表达的作用.北京中医药大学学报,2003,26(3)：18-20.
[42]赵红念,胡晓松,周东,等.三七三醇皂苷对局灶性脑缺血再灌注大鼠脑组织Nestin表达的影响.华西医学,2005,20(2)：297-299.
[43]余鸿,刘敦玉,吴雨岭,等.当归对缺氧鼠胚模型神经干细胞增殖的影响[J].中国现代医学杂志,2005；21(15)：3226-3228.
[44]崔桂云,沈霞,张璐,等.丹参神经保护作用机制的研究[J].徐州医学院学报,2002；22(6)：492-494
[45]高中洪,黄开勋,徐辉碧.黄芩黄酮对H202导致的神经细胞损伤的保护作用[J].中国药理学通报,2000;16(5)：589-590
[46]杨娟,陈付学,梁光义.刺梨多糖对神经干细胞谷氨酸损伤的保护作用.营养学报,2005,27(4)：339-341.
[47]刘柏炎,黎杏群,张化先,等.脑溢安颗粒对实验性大鼠脑出血后神经干细胞增殖的影响.中国临床康复,2003,7(25)：3428-3429.
[48]武衡,黎杏群,唐涛,等.脑溢安对大鼠海马神经干细胞分化的影响.中国临床康复,2004,8(28)：6148-6149.
[49]罗杰坤,黎杏群,刘柏炎,等.脑溢安对大鼠缺氧神经干细胞保护作用.中国临床康复,2004,8(22)：4534-4535.
[50]肖岚,黎杏群,刘柏炎,等.脑溢安对新生大鼠海马神经干细胞缺氧损伤及p38MAPK活性的影响.中国现代医学杂志,2004,14(16)：67-74.
[51]刘柏炎,蔡光先.补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响.中国药物与临床,2005,5(3)：171-173.
[52]蔡光先,刘柏炎.补阳还五汤对体外低糖低氧损伤海马神经干细胞增殖的影响. 湖南中医学院学报,2005,25(2)：1-3.
[53]刘柏炎,蔡光先,林琳,等.补阳还五汤对大鼠局灶性脑缺血后神经干细胞影响的初步研究.中国临床康复,2004,8(22)：4532-4533.
[54]高唱,王景周.左归丸对体外培养新生大鼠海马神经干细胞增殖分化的影响.中国医药学报,2004,19(11)：691-693.
[55]杨萍,王继明,应大君,等.中药制剂—肌萎灵注射液对神经干细胞的促分化作用.神经解剖学杂志,2005,21(2)：171-174.
[56]卢昌均,陆兵勋,王立新,等.缺血后再灌注损伤大鼠脑内β2微管蛋白的变化及通心络对其影响.中国急救医学,2006,26(1)：44-45.
[57]刘倩.脑出血的中西医结合研究进展(综述)[J].中国中西医结合急救杂志,2008,(15)6：381-384.
[58]杨宏勇.脑出血急性期阳闭证中医论治的思路及方法探析[J].中国中医急症,2009,18(4)：564-565.
[59]戴高中.陈汝兴.顾明昌等.大黄廑虫丸对大鼠脑出血模型神经损伤积分值和脑组织凝血酶受体mRNA表达的影响[J].辽宁中医杂志,2007,34(6)：838-841.
[60]戴高中.陈汝兴.顾明昌等.大黄麈虫丸对大鼠脑出血模型脑组织IL-1BmRNA、 NO2mRNA表达的影响[J].四川中医,2008,26(2)：18-20.
[61]张小萍.吴颢昕.刘韶华等.抵当口服液对大鼠脑出血模型C-fos蛋白表达及脑水肿指数的影响[J].中国中医急症,2007,16(5)：579-580.
[62]罗杰坤.唐涛.黎杏群等.补阳还五汤对脑出血大鼠脑内Caspase-3活化的影响[J].湖南中医学院学报,2006,26(3)：12-141.
[63]王玲.唐涛.罗杰坤等.补阳还五汤对脑出血大鼠脑内MMP2表达的影响[J].中国老年学杂志,2007,27(7)：1257-12601.
[64]高志荣.凉血化瘀法对大鼠脑出血的实验研究[J].中国中医急症,2006,15(10)：1131-1132.
[65]秦峰.王长松.晋光荣等.犀角地黄汤对大鼠脑出血后脑水肿及行为学影响的研究[J].中国中医急症,2008,17(6)：801-803.
[66]范录平.叶华.郭蕾等.卒中散对脑出血大鼠抓握能力的改善及血清S100B水平的影响[J].实用中西医结合临床,2007,7(2)：9-10.
[67]赵清超.胡久略.活血通窍贴片经皮给药对兔急性脑出血血液流变学及超氧化 物歧化酶、丙二醛的影响[J].中国临床药理学与治疗学,2008,13(7)：772-775.
[68]刘淑霞.聂伟.杜婴等.黄竹清脑口服液对急性脑出血大鼠血清中CRP及脑组织中MDA GSH-PX的影响[J].辽宁中医杂志,2008,35(12)：1936-1937.
[69]刘淑霞.白雅.任惠锋等.黄竹清脑颗粒对痰热腑实证脑出血急性期大鼠血清MDA及血浆TNF的影响[J].江西中医学院学报,2009,21(2)：62-64.
[70]王长松.晋光荣.张斌霞等.下瘀清痰汤对脑出血后脑水肿影响的实验研究[J].辽宁中医学院学报,2006,8(3)：119-120.
[71]侯俊良.梁清华.包太成等.大承气汤对脑出血大鼠神经元线粒体内细胞色素C释放的影响[J].实用预防医学,2006,13(3)：495-498.
[72]张国平.刘华.别晓东等.通腑活血汤对脑出血大鼠脑组织保护作用的病理实验研究[J].广东医学,2006,8：1152-1153.
[73]杨琴芳.许毅.秦峰等.桃核承气汤对大鼠脑出血急性期Bcl-2、Bax蛋白表达的影响[J].南京中医药大学学报,2009,25(4)：281-282.
[74]陆红.王桂敏.逐淤化痰汤对脑出血大鼠脑含水量及SOD活性的影响[J].辽医学院学报,2009,30(1)17-19.
[75]杨文清.任玉录.郭克锋等.安宫牛黄丸对急性脑出血大鼠脑组织中一氧化氮合酶及单胺类神经递质的影响[J].中国中医急症,2009,18(1)：83-84.
[76]付宪文.孙异临.党国义等.安宫牛黄丸对脑出血大鼠脑组织超微结构的影响[J].河北中医药学报,2008,23(1)：39-41.
[77]李鹏英.鲁艺.刘敏等.新清开灵注射液对大鼠脑出血后脑组织SOD、脑含水量的影响[J].山东中医杂志,2007,26(2)：116-117.
[78]周庆博.李鲁扬.贾青等.清热解毒法对脑出血大鼠的神经保护作用[J].山东大学学报(医学版),2007,45(9)：947-950.
[79]杨仲义.史载祥.方芳等.羚黄汤对实验性大鼠脑出血损伤的保护作用[J].中国中医急症,2007,16(4)：451-452.
[80]杜宝新.郑国庆.卢明等.脑脉Ⅱ号胶囊抑制脑出血后脑水肿的机理研究[J].广州中医药大学学报,2007,24(4)：297-399.
[81]何纲.黄培新.刘茂才等.脑脉Ⅱ号口服液对高血压脑出血大鼠血肿周围组织半胱氨酸天冬氨酸特异性蛋白酶-3活性和细胞凋亡的影响[J].实用医学杂志,2009,25(10)：1573-1575.
[82]陶双友.刘茂才.卢明等.脑脉Ⅱ号胶囊对脑出血所致脑心综合征大鼠心电图的影响[J].时珍国医国药,200617(3)：323-324.
[83]熊新贵.梁清华.包太成.不同中医治法对实验性脑出血大鼠Caspase-3表达的影响[J].实用预防医学,2007,14(1)：13-15.
[84]萧梅芳.梁清华.谭勇等.不同中医治法对脑出血大鼠神经元损伤及海马线粒体膜电位的影响[J].实用预防医学,2007,14(5)：1347-1349.
[85]张雨星.梁清华.谭勇等.不同中医治法对脑出血大鼠海马线粒体DNA含量的影响[J].湖南中医药大学学报,2007,27(5)：32-35.
[86]齐勇.唐涛.罗杰坤等.益气活血法对脑出血大鼠脑内TSP-1、TSP-2及其受体CD36表达的影响[J].中国老年学杂志,2007,27(10)：913-916.
[87]杨继文.王威.袁曙光等.黄芪合丹参注射液对急性脑出血大鼠神经细胞凋亡表达的影响[J].中华中医药杂志(原中国医药学报),200722(10)：720-722.
[88]聂亚雄.霍瑞民.赵强等.三七总皂苷分期治疗对脑出血大鼠微管相关蛋白-2及神经生长相关蛋白表达的影响[J].中西医结合心脑血管病杂志,2009,7(5)：547-549.
[89]霍瑞民.聂亚雄.姜波涛等.三七总皂苷对大鼠脑出血后肢体功能和MAP-2及GAP-43表达水平的影响[J].中西医结合心脑血管病杂志,2008,6(2)：168-170.
[90]聂亚雄.尹剑.朱文龙等.三七总皂苷注射液对脑出血大鼠颅内血肿及脑水肿的影响[J].湖南中医药大学学报,200929(3)：37-39.
[91]郭志松.邵换璋等.三七总皂甙对脑出血大鼠的神经保护作用[J].中国实用神经疾病杂志,2009,12(11)：42-44.
[92]周秀丽.曾光伟.李士坤等.B-七叶皂甙钠对脑出血大鼠的神经保护作用[J].中国实用神经疾病杂志,2008,11(4)：27-29.
[93]罗琳.雷久士.亚低温合七叶皂苷钠对大鼠脑出血后血肿周围Bax、Bcl-2表达的影响[J].湖南中医药大学学报,2007,27(2)：50-53.
[94]周天梅.黄晓明.韦志盖等.川芎嗪注射液治疗急性期脑出血大鼠的时间窗研究[J].中国中医急症,2009,18(1)：81-82.
[95]吴瑛.任安乐.大鼠脑出血急性期给予水蛭素后血肿周围组织胶质纤维酸性蛋白的表达[J].兰州大学学报(医学版),2009,35(1)：1-4.
[96]杨文海.宁显忠.王媛媛等.核转录因子KB在大鼠脑出血后血肿周围组织中的表达及水蛭素的保护作用[J].中西医结合心脑血管病杂志,2006,(12)：1436-1437.
[97]杨奎.闵志强.石娅萍等.栀子总环烯醚萜苷对脑出血大鼠炎症反应与神经元凋亡的影响[J].中药新药与临床药理,2009,20(1)：8-10.
[98]周乾坤.余嗣明.刘平等.黄芩苷对脑出血大鼠脑内氨基酸递质含量的影响.[J].中国中医药信息杂志,200916(4)：35-37.
[99]刘平.隗义双.周乾坤等.黄芩苷对实验性脑出血大鼠脑损伤的保护作用[J].中国中医药信息杂志,2008,15(4)：34-35.
[100]黄良国.王东.葛正龙等.刺五加对大鼠脑出血病理变化及13-EP的影响[J].中国老年学杂志,2006,26(9)：1232-1234.
[101]殷利春.杜抗根.何民等.葛根素对实验性脑出血大鼠偏瘫状态和脑组织NO含量的影响[J].中国中医药科技,2007,14(3)：173-174.
[102]张海宇.马全瑞.张莲香等.黄芪注射液对大鼠脑出血灶周围神经元超微结构的影响[J].解剖学杂志,2009,32(3)：3308-3311.
[103]许东.胡治平.秦毅等.黄芪注射液对脑出血大鼠细胞凋亡影响的研究[J].临床神经病学杂志,2008,21(1)：37-40.
[104]于君.周庆博.毕建忠等.蚤休和半边莲对大鼠脑出血后血浆细胞间黏附分子-1肿瘤坏死因子-OL的影响[J].中医药学刊,2006,24(10)：1910-1912.
[105]郑国庆.王艳.黄培新等.脑血康对急性脑出血大鼠脑组织超微结构的影响[J].中医药学刊,2006,24(5)：835-838.
[106]赵佳辉.针刺对脑出血大鼠兴奋性氨基酸含量影响的研究[J].新医学导刊,2008,7(2)：7-9.
[107]姜桂关.针刺对脑出血模型大鼠急性期血肿周围脑组织IL-113及IL-6的影响[J].广东医学,2009,30(7)：1045-1047.
[108]李奎生.论活血化瘀法在中风治疗中的地位[J].现代中西医结合杂志,2004,13(13)：1082-1083.
[109]郑国庆.出血中风急性期的治则治法阐发[J].中国医药导报,2006,17：256.
[110]张宪忠,孙宝红.急性脑卒中超早期中西医结合抢救治疗的思考[J].中国中西医结合急救杂志,1998,5(2)：49-51.
[111]刘泰.对急性脑出血脑水肿期中医病机的探讨[J].中华实用中西医志,2001,14(22)：2179.
[112]姜春华.活血化瘀研究新编[M].上海：上海医科大学出版社,1990：139.
[113]杨万章.逐瘀化痰汤对脑出血患者颅内血肿及血液流变学的影响[J].中医杂志,1996,37(1])：670.
[114]高慧娟,黄永勤,李新毅.影响急性脑出血患者血液流变学的因素分析[J].临床医学,2006,26(1)：3-5.
[115]姜兆顺.2型糖尿病血瘀证患者血小板CD62P、CD63测定意义探讨[J].中国中西医结合杂志,1999,19(9)：527.
[116]石志芸.血瘀证患者血小板α-颗粒膜蛋白、内皮素测定[J].中医杂志,1996,37(4)：239.
[117]唐宇平,蔡定芳,刘军,等.大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究[J].中国中西医结合杂志,2006,26(2)：152-156.
[118]刘泰.传统方剂五苓散加减后2种复方制剂对细胞毒性脑水肿的作用[J].中国临床康复,2006,10(11)：53-55.
[119]刘泰.传统方剂五苓散加减后的2种复方制剂对血脑屏障保护作用比较[J].中国临床康复,2006,10(15)：168-170.
[120]张永全,刘泰,陆晖,等.健神利水Ⅰ号对脑出血急性期血液流变性及超氧化物歧化酶的影响[J].中国中西医结合急救杂志,2002,9(5)：273-275.
[121]刘泰,甘照儒,陆晖,等.健神利水Ⅰ号治疗脑出血急性期脑水肿60例临床研究[J].中医杂志,2003,44(2)：103.
[122]张永全,刘泰,陆晖,等.健神利水Ⅰ号对脑出血急性期脑水肿的临床疗效[J].广西中医药,2002,25(5)：8.
[123]顾宁,王长松,周仲瑛.凉血通瘀注射液对急性脑出血患者近期疗效的影响[J].新中医,2007,39(1)：40-41.
[124]高树良,王晋朝,陈玉芹.利水逐瘀法治疗高血压性脑出血颅内压增高临床研究[J].河北中医,2002,24(4)：243-245.
[125]户文娟,杨际清.脑出血继续出血68例临床分析[J].中西医结合心脑血管病杂志,2004,2(1)：56-57.
[126]李铁山,韩仲岩.脑出血继续出血及其影响因素[J].国外医学：脑血管疾病分册,1999,7(2)：96.
[127]杨万章.出血性中风活血化癖法应用时间窗探讨[J].中国医药学报,2002,17(12)：743-745.
[128]常诚.脑出血活血化瘀治疗的影响因素[J].河北中医杂志,2003,25(3)：192-193.
[129]杨仲义,史载祥.活血化瘀法治疗高血压急性脑出血探讨[J].中国中医药信息杂志,2007,14(5)：89-90.
[130]赵耀东,李军.活血化瘀与脑出血急性期[J].甘肃中医学院学报,2002,19(4)：8.
[131]严容,张钟爱.活血化瘀法在出血性中风急性期的运用及常见问题探讨[J].江西中医学院学报,2006,18(4)：11.
[132]刘清泉,安海燕,郭建文.分层扭转法与脑出血重症[J].中国医药学报,1999,14(2)：54.
[133]朱东胜,徐敏华,卫洪昌,等.中风系列制剂治疗急性脑出血的临床与试验研究[J].中国中西医结合急救杂志,2000,7(3)：133-136.
[134]黄坚红,陈秀慧,刘健红.分期选用活血化瘀药治疗高血压性脑出血32例疗效观察[J].新中医杂志,2005,37(11)：30-31.
[135]杨继文,袁曙光,多慧玲.补阳还五汤加减治疗中小量脑出血急性期30例临床观察[J].河北中医杂志,2004,26(11)：841-842.
[136]张爱华.黄芪在脑出血中应用50例疗效观察[J].中国误诊学杂志,2002,2(9)：1351.
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