脑立轻胶囊对拟血管性痴呆大鼠空间学习记忆影响的研究
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摘要
血管性痴呆(vascular dementia,VD)系指在各种脑血管疾病基础上引起的脑组织损害,并产生以高级神经认知功能障碍为主的一组临床综合征,是老年期痴呆的主要类型之一,临床主要表现为认知功能、社会生活能力的减退及情感性格的改变等症状,学习记忆能力受损突出,致残率高,严重影响患者的生活质量,造成了沉重的经济和社会负担。现代医学对该病尚无特效治疗手段,长期治疗费用昂贵。
随着近年来中医药基础和临床研究的深入,中医药在防治VD上日益显示出优势。脑立轻胶囊根据VD多以“肾精亏虚、瘀阻脑脉”为其主要病机特点,以“补益肾精、化瘀通络”为其治则,用肉苁蓉、山茱萸、三七、银杏叶、葛根组方而成,在临床中取得了较好疗效。本课题通过动物实验方法研究脑立轻胶囊对拟VD大鼠空间学习记忆的影响,探讨其作用机制,为临床用本药治疗VD提供理论依据。
实验研究分为以下3部分:
1选用清洁级雄性SD大鼠80只,双侧颈总动脉永久性结扎法(2-VO)建立VD大鼠模型,造模后动物随机分为脑立轻胶囊高、中、低剂量组和模型组、假手术组、对照组,每组10只。对照组选用尼麦角林作为对照药物,动物灌胃给药,治疗期30天。
2治疗期结束后行Morris水迷宫实验,通过定位航行实验、空间探索实验、可见平台实验,检测治疗后模型大鼠的空间学习记忆能力,比较各组之间成绩的差异。从行为学上观察脑立轻胶囊对拟VD大鼠记忆的影响,探讨其治疗作用。
3采用4%多聚甲醛经心脏灌注,待鼠尾变硬后取脑,石蜡包埋、切片,HE染色观察各组大鼠海马CA1区锥体细胞形态变化,计数锥体细胞,比较脑立轻胶囊对大鼠海马CA1区锥体细胞的影响;免疫组化法检测各组大鼠海马CA1区与记忆关系密切的酶-胆碱乙酰转移酶(ChAT)和与突触相关蛋白-突触素(Syn)的表达,比较组间差异,探讨脑立轻胶囊对ChAT和Syn表达的影响。
大鼠经2-VO法造模70只,术后3天死亡19只;假手术组造模10只,无死亡。实验期间又陆续死亡6只。实验结果显示造模后各组大鼠的水迷宫成绩较假手术组明显下降(p＜0.01),海马CA1区锥体细胞的计数及胆碱乙酰转移酶(ChAT)和突触素(Syn)的表达与假手术组比较亦具有显著性差异(p＜0.01),说明经2-VOS法造模后大鼠的行为学成绩、海马CA1区锥体细胞及相关蛋白明显下降,证实造模成功。高剂量组和对照组的各项结果相比较无显著性差异(p＞0.05),高剂量组与模型组及低剂量组结果相比较具有显著性差异(p＜0.01),而低剂量组与模型组各项结果比较改善不明显(p＞0.05),中剂量组的各项结果介于高低剂量之间。
实验结果说明双侧颈总动脉永久性结扎(2-VO)造成了大鼠学习记忆障碍和脑组织病理形态以及相关蛋白的改变,证明模型成功。中药脑立轻胶囊可以改善拟VD大鼠的空间学习记忆能力,其机制可能是:对低灌注环境下的大鼠海马CA1区神经元具有保护作用,减轻缺血对其造成的损伤;抑制缺血后模型大鼠海马CA1区ChAT和Syn的降低,提高模型大鼠海马CA1区ChAT和Syn表达,改善胆碱能神经元的功能,促进突触重塑;实验结果与剂量有关,高剂量明显优于中剂量和低剂量。同时也从动物实验证实脑立轻胶囊治疗VD确有疗效,但该药保护锥体细胞和对ChAT及Syn表达影响的具体机制有待进一步研究。
Vascular dementia(VD)is an impairment of cognitive function caused by cerebrovascular disease,which is one of the main styles of the aged dementias. Cognitive impairment,decreased the ability of memory and change of the Psychological signs are its main clinical manifestation.Although there is not VD's name in traditional Chinese medicine(YCM),VD belongs to "idiotia","foolish disease","stupid disease","mind disease","dementia","depressed syndrome" in TCM age-old record.Owing to so high incidence of VD,and it has the high incidence of Mutilation disease.the quality of life is affected seriously,which further results in great social and family burden.
The modem medicine has maken great development in VD,many researches have been made on VD,but there is not effective methods and medicine for VD.To control the development of pathogenetic condition and to improve brain function and quality of life are main goals of treatment on clinically,and it will spend much expense for long term therapy.Recently,as more and more basic and clinic researches on Traditional Chinese Medicine(TCM)treating VD have been made,more and more privileges have appeared,k is significant for adopting traditional Chinese drug to treat VD.TCM has accumulated a lot of experience.Naoliqing capsule is according to that "deficiency of kidney-essence,obstruction of collaterals by blood stasis" is one of the main pathogenesis of VD and the therapeutical principle of VD should be "tonified kidney-essence,disperse blood stasis and dredge collateral" on the basis of clinical experience.Naoliqing capsule is made from Desertliving Cistanche,Asiatic Cornelian Cherry Frui,Sanchi,ginkgo leaf,Kudzuvine Root.Through animal experiment to expound the pharmacology of Naoliqing,we will reveal the mechanism how Naoliqing treat VD.Therefore,we established VD animal model to estimate the effects of cognitive dysfunction with Naoliqing treatment fromethology and histomorphology.
The experiment is departed into three parts:
1 This topic Chooses healthy male SD rats to established VD animal model.The rat models of vascular dementia were made by permanent bilateral occlusion of both commen carotid arteries(2-VO),the models were divided into six groups at random: sham-operated group,model group,nicergoline group and Naoliqing large, medium、small dose group.the medicine was given to the models by intragastric administration.
2 Testing learning and memory by Morris water-maze when models were treated for 30 days.
3 Fixed up via perfusion of 4%paraformaldehyde solution,brain samples with HE staining and immunohistorychemistry were applied to analyze the state of pyramidal cell and expression of ChAT and Syn.Take count of the cells and Observe the appearance of acethylcholine ChAT and Syn in CA1 district in hippocampus and compare it.
We take the Escape latency of MWM as the evaluation target.Compared with model group,the large dose group and nicergoline group's escape incubation period is shorter(P＜0.01);compared with small group,the large group and medium group's escape incubation period were shorter(P＜0.01).The quantity of pyramidal cells in hippocampal CA1 region in model group was significantly less than other group's. The large group's and The medium group's the positive expression of ChAT and Syn in hippocampal CA1 region is significantly higer than model group and small dose group(P＜0.01).there was no significantly difference between small dose group and model group(P＞0.05).
The Results of experiment shows that:2-VO could cause the impairment of learning and memory ability of model rats and brain tissue degeneration of VD model rats,so it succeeded in establishing VD animal models.Treating VD rats with Naoliqing capsule can obviously improve the function of spatial learning and memory of VD animal models,alleviating the impairment of neuron ischemia in the hippocampal CA1 region and enhance expression of ChAT and Syn in hippocampal CA1 region maybe the histopathological base for improving the cognitive dysfunction of VD rats.
随着近年来中医药基础和临床研究的深入,中医药在防治VD上日益显示出优势。脑立轻胶囊根据VD多以“肾精亏虚、瘀阻脑脉”为其主要病机特点,以“补益肾精、化瘀通络”为其治则,用肉苁蓉、山茱萸、三七、银杏叶、葛根组方而成,在临床中取得了较好疗效。本课题通过动物实验方法研究脑立轻胶囊对拟VD大鼠空间学习记忆的影响,探讨其作用机制,为临床用本药治疗VD提供理论依据。
实验研究分为以下3部分:
1选用清洁级雄性SD大鼠80只,双侧颈总动脉永久性结扎法(2-VO)建立VD大鼠模型,造模后动物随机分为脑立轻胶囊高、中、低剂量组和模型组、假手术组、对照组,每组10只。对照组选用尼麦角林作为对照药物,动物灌胃给药,治疗期30天。
2治疗期结束后行Morris水迷宫实验,通过定位航行实验、空间探索实验、可见平台实验,检测治疗后模型大鼠的空间学习记忆能力,比较各组之间成绩的差异。从行为学上观察脑立轻胶囊对拟VD大鼠记忆的影响,探讨其治疗作用。
3采用4%多聚甲醛经心脏灌注,待鼠尾变硬后取脑,石蜡包埋、切片,HE染色观察各组大鼠海马CA1区锥体细胞形态变化,计数锥体细胞,比较脑立轻胶囊对大鼠海马CA1区锥体细胞的影响;免疫组化法检测各组大鼠海马CA1区与记忆关系密切的酶-胆碱乙酰转移酶(ChAT)和与突触相关蛋白-突触素(Syn)的表达,比较组间差异,探讨脑立轻胶囊对ChAT和Syn表达的影响。
大鼠经2-VO法造模70只,术后3天死亡19只;假手术组造模10只,无死亡。实验期间又陆续死亡6只。实验结果显示造模后各组大鼠的水迷宫成绩较假手术组明显下降(p＜0.01),海马CA1区锥体细胞的计数及胆碱乙酰转移酶(ChAT)和突触素(Syn)的表达与假手术组比较亦具有显著性差异(p＜0.01),说明经2-VOS法造模后大鼠的行为学成绩、海马CA1区锥体细胞及相关蛋白明显下降,证实造模成功。高剂量组和对照组的各项结果相比较无显著性差异(p＞0.05),高剂量组与模型组及低剂量组结果相比较具有显著性差异(p＜0.01),而低剂量组与模型组各项结果比较改善不明显(p＞0.05),中剂量组的各项结果介于高低剂量之间。
实验结果说明双侧颈总动脉永久性结扎(2-VO)造成了大鼠学习记忆障碍和脑组织病理形态以及相关蛋白的改变,证明模型成功。中药脑立轻胶囊可以改善拟VD大鼠的空间学习记忆能力,其机制可能是:对低灌注环境下的大鼠海马CA1区神经元具有保护作用,减轻缺血对其造成的损伤;抑制缺血后模型大鼠海马CA1区ChAT和Syn的降低,提高模型大鼠海马CA1区ChAT和Syn表达,改善胆碱能神经元的功能,促进突触重塑;实验结果与剂量有关,高剂量明显优于中剂量和低剂量。同时也从动物实验证实脑立轻胶囊治疗VD确有疗效,但该药保护锥体细胞和对ChAT及Syn表达影响的具体机制有待进一步研究。
Vascular dementia(VD)is an impairment of cognitive function caused by cerebrovascular disease,which is one of the main styles of the aged dementias. Cognitive impairment,decreased the ability of memory and change of the Psychological signs are its main clinical manifestation.Although there is not VD's name in traditional Chinese medicine(YCM),VD belongs to "idiotia","foolish disease","stupid disease","mind disease","dementia","depressed syndrome" in TCM age-old record.Owing to so high incidence of VD,and it has the high incidence of Mutilation disease.the quality of life is affected seriously,which further results in great social and family burden.
The modem medicine has maken great development in VD,many researches have been made on VD,but there is not effective methods and medicine for VD.To control the development of pathogenetic condition and to improve brain function and quality of life are main goals of treatment on clinically,and it will spend much expense for long term therapy.Recently,as more and more basic and clinic researches on Traditional Chinese Medicine(TCM)treating VD have been made,more and more privileges have appeared,k is significant for adopting traditional Chinese drug to treat VD.TCM has accumulated a lot of experience.Naoliqing capsule is according to that "deficiency of kidney-essence,obstruction of collaterals by blood stasis" is one of the main pathogenesis of VD and the therapeutical principle of VD should be "tonified kidney-essence,disperse blood stasis and dredge collateral" on the basis of clinical experience.Naoliqing capsule is made from Desertliving Cistanche,Asiatic Cornelian Cherry Frui,Sanchi,ginkgo leaf,Kudzuvine Root.Through animal experiment to expound the pharmacology of Naoliqing,we will reveal the mechanism how Naoliqing treat VD.Therefore,we established VD animal model to estimate the effects of cognitive dysfunction with Naoliqing treatment fromethology and histomorphology.
The experiment is departed into three parts:
1 This topic Chooses healthy male SD rats to established VD animal model.The rat models of vascular dementia were made by permanent bilateral occlusion of both commen carotid arteries(2-VO),the models were divided into six groups at random: sham-operated group,model group,nicergoline group and Naoliqing large, medium、small dose group.the medicine was given to the models by intragastric administration.
2 Testing learning and memory by Morris water-maze when models were treated for 30 days.
3 Fixed up via perfusion of 4%paraformaldehyde solution,brain samples with HE staining and immunohistorychemistry were applied to analyze the state of pyramidal cell and expression of ChAT and Syn.Take count of the cells and Observe the appearance of acethylcholine ChAT and Syn in CA1 district in hippocampus and compare it.
We take the Escape latency of MWM as the evaluation target.Compared with model group,the large dose group and nicergoline group's escape incubation period is shorter(P＜0.01);compared with small group,the large group and medium group's escape incubation period were shorter(P＜0.01).The quantity of pyramidal cells in hippocampal CA1 region in model group was significantly less than other group's. The large group's and The medium group's the positive expression of ChAT and Syn in hippocampal CA1 region is significantly higer than model group and small dose group(P＜0.01).there was no significantly difference between small dose group and model group(P＞0.05).
The Results of experiment shows that:2-VO could cause the impairment of learning and memory ability of model rats and brain tissue degeneration of VD model rats,so it succeeded in establishing VD animal models.Treating VD rats with Naoliqing capsule can obviously improve the function of spatial learning and memory of VD animal models,alleviating the impairment of neuron ischemia in the hippocampal CA1 region and enhance expression of ChAT and Syn in hippocampal CA1 region maybe the histopathological base for improving the cognitive dysfunction of VD rats.
引文
[1]Ferri CP,Prince M,Brayne C,et al.Global prevalence of dementia:a Delphi consensus study[J].Lancet,2005,366(9503):2112-2119.
[2]柄澤昭秀.痴呆の疫学[J].治療,2004,86:11-15.
[3]Zhang ZX,Zahner GEP,Roman GC,et al.Dementia subtypes in China:prevalence in Beijing,Xian,Shanghai,and Chengdu[J].Arch Neurol,2005,62(3):447-453.
[4]朱飞奇,王正君,张海燕.王正君治疗血管性痴呆的临床经验[J].中国中医药信杂志,2004,11(2):169.
[5]赵宪林,方秀斌,李东培.大鼠血管性痴呆模型制作[J].中国医科大学学报,2002,31(3):166-168.
[6]林海,张壮,孙塑伦 等.拟血管性痴呆大鼠造模中应注意的几点问题[J].中医药学刊.2005,23(4):625-627.
[7]Morris R.Developments of a water-maze procedure for studying spatial learning in the rat[J].J Neurosci Methods,1984,11(1):47-60.
[8]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探[J].广州中医药大学学报[J],2000,17(2):117-119.
[9]李甘地 主编.组织病理技术[M].北京:人民卫生出版社,2002.
[10]田金洲,王永炎,刘峘 等.血管性痴呆发病机理研究[J].中医杂志,2003,44(8):565.
[11]赵勇,崔淑芳,汤球.血管性痴呆动物模型研究进展[J].上海实验动物科学,2005,25(1):54-58.
[12]de laTorre JC,Fortin T,Park GA et al.Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.Brain-Res,1992;582(2):186-195.
[13]Olsson Y,Brun A,Engiuund E.Fundamental pathological lesions in vascular dementia[J].Acta Neurol Scand Suppl,1996,168:31-38.
[14]李巍,张世仪。小鼠脑缺血性学习记忆障碍模型的建立[J].基础医学与临床,1995,15(6):46-49.
[15]刘汇波,叶翠飞,李斌 等.双侧颈总动脉结扎对大鼠学习记忆功能和海马组织形态学的影响[J],基础医学与临床,1998,18(4):54-58.
[16]Devan BD,Goad EH,Petri HL.Dissociation of hippocampal and striatal contributions to spatial navigation in the water maze.Neurobiol Learn Mem,1996,66(3):305-323.
[17]Tsuchiya M,Sako K,Yura S,et al.Local cerebral glucose utilization following acute and chronic bilateral carotid artery ligation in Wistar rats:relation to changes in local cerebral blood flow[J].Exp Brain Res,1993,95(1):1-8.
[18]Nanti M,Watanabe H.Availability of 2-V0 rats as a model for chronic cerebrovascular disease[J].Nippon Yakurigaku Zasshi,1999,113(2):85-95.
[19]Pappas BA,de la Torte JC,Davidson CM,el al.Chronic reduction blood flow in the adult rat:late-emerging CA1 cell loss and memory dysfunction[J].Brain Res,1996,708(1-2):50-58.
[20]Watanabe H,Ni HW,Sakai Y,et al.Permanent occlusion of bilateral internal carotid arteries produces cognitive deficits in two learning behavior tasks[J].Nihon Shinkei Seishin YakurigakuZasshi,1996,16(1):19-24.
[21]Myron D,Ginsberg N,Raul B.Rodent models of cerebral ischemia[J].Stroke,1989,20:1627-1642.
[22]Pulsinelli WA,Brierley JB.A new model of bilateral hemispheric ischemia in the unanesthetized rat[J].Stroke,1979,10(3):267-272.
[23]王蕊,杨秦飞,唐一鹏等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10):914-916.
[24]高东,周中和.实验性血管性痴呆的模型制作问题[J].国外医学·老年医学分册,2003,23(2):59-61.
[25]李巍,张世仪,赵惠敏 等.小鼠缺血性学习记忆障碍模型的建立[J].基础医学与临床,1995,15(6):46.
[26]唐启盛,黄启福,郭建文.高脂血症大鼠缺血再灌流诱发行为学障碍模型的实验研究[J].北京中医药大学学报,1997,20(5):34.
[27]王蕊,杨秦飞,庸鹏 等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10):914.
[28]林监,王子栋.血管性痴呆动物模型[J].中国应用生理学杂志,1998,14(1):89.
[29]梅建勋,张云岭,张伯礼 等.多发梗塞性痴呆人鼠模型的改进与应用[J].中国中西医结合杂志,2000,20(2):113.
[30]Takagi K,Takeo S.The model of stroke induced by microsphere embolism in rats[J].Nippon YakurigakuZasshi,2003,121(6):440-446.
[31]腾晶.康脑灵Ⅱ号治疗血管性痴呆实验与临床研究[J].山东中医药大学学报,2000,24(1):48.
[32]韩冬,廖福龙,李文 等.冷光源光化学诱导局灶性脑梗塞及血管损伤半暗带大鼠模型[J].中国微循环,2001,5(1):71.
[33]陈春富,郭述苏.大鼠局灶性脑缺血模型研究进展[J].国外医学·脑血管疾病分册,1995,3(5):227.
[34]Sabbatini M,Catalani A,Consoli C,et al.The hippocampus in spontaneously hypertensive rats:an animal model of vascular dementia[J].Mech Ageing Dev,2002,23(5):54-75.
[35]Saito H,Togashii H,Yoshioka M,et al.Animal model of vascular dementia with emphasis on stroke-prone spontaneously hypertension rats[J].Clin Exp Pharmacol Physiol,1995,22(1):257-266.
[36]陈惟昌,于萍,李占魁等.破坏海马角CA3区后小鼠记忆动力学变化[J].中日友好医院学报,1996,10(2):95.
[37]王浴生,邓文龙,薛春生.中药药理与应用[M].人民卫生出版社,北京,第二版,2000.
[38]张扩建.银杏叶治疗老年脑血管疾病临床研究[J].中成药.2005,27(9):1053-1055.
[39]吴海琴,张蓓,张桂莲 等.葛根素对脑缺血再灌注损伤的保护作用[J].卒中与神经疾病,2005,12(4):209-211.
[40]张冰清,王玉良.葛根素对血管性痴呆大鼠海马锥体细胞和BDNF表达的影响[J].神经解剖学杂志,2007,23(6):615-620.
[41]蒋晓燕,王晓雯,王雪飞 等.肉苁蓉总苷对大鼠局灶性脑缺血损伤的影响[J].中草药,2004,35(6):660-662.
[42]皋聪,王传社,巫冠中 等.苁蓉总甙对血管性痴呆大鼠学习记忆的影响及机制研究[J].中草药,2005,12(36):1852-1854.
[43]杨晋,陈随清,冀春茹 等.山茱萸化学成分的分离鉴定[J].中草药,2005,36(12):1780-1782.
[44]藏连碧,郑怡建.山茱萸抗衰老实验研究[J].浙江中医学院学报,1993,17(5):34.
[45]苗明三,杨云.山茱萸多糖抗氧化作用研究[J].河南中医,2002,22(1):66-67.
[46]沈映君 主编.中药药理学.上海:上海科学技术出版社.1997.
[47]郭长杰,伍杰雄,李若馨.三七总皂苷对痴呆模型大鼠大脑皮质内神经递质含量的影响[J].中国临床药学杂志.2004,13(3):150-152.
[48]钟振国,屈泽强,王乃平 等.三七总皂苷对大脑基底核损伤动物模型大脑神经元突触素的影响[J].中国中药杂志,2005,30(12):913-915.
[49]卢家红,吕传真,洪震 等.尼麦角林治疗血管性痴呆的前瞻性、双盲、多中心研究[J].中华神经科杂志,2001,34(2):88-91.
[50]叶莉英,翟金霞,高建国.尼麦角林治疗脑血管病伴记忆功能障碍50例疗效观察[J].临床神经病学杂志,2004,17(2):142-143.
[51]Morris R GM,Garrud P,Rawlins J NP,et al.Place nayigation impaired in rats with hippocampallesions[J].Nature,1982,297:681-684.
[52]关新民.医学神经生物学纲要[M].北京:科学出版社.2003.
[53]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探.广州中医药大学学报,2000,17(2):117-119.
[54]Gandhi CC,Kellyl RM,Wiley RG,et al.Impaired acquisition of a Morris water maze task following selective destruction of cerebellar Purkinje cells with 0X7-saporin.Behav Brain Res,2000;109(1):37-47.
[55]韩太真,吴馥梅.学习与记忆的神经生物学[M].北京:北京医科大学、中国协和医科大学联合出版社,1998,162-177.
[56]Kirino.Delayed neuronal death in the gerbil hippocampus following ischemia[J].Brain Res,1982,239:57-69.
[57]de-la-Torre,JC;Fortin,T;Park,GA;et al.Brain blood flow restoration rescues chronically damaged rat CA1 neurons[J].Brain-Res,1993:623(1):6-15.
[58]Akhondzadeh S.Hippocampal synaptic plasticity and cognition[J].J Clin Pharmacol Ther,1999;24(4):241-249.
[59]Whishaw IQ,Rod MR,Auer RN.Behavioral deficits revealed by multiple tests in rats with ischemic damage limited to half of the CA1 sector of the hippocampus[J].Brain Res Bull.1994;34(3):283-292.
[60]Nelson A,Lebessih,Sowinski P,et al.Comparison of effects global cerebral ischemia on spatial learning in the standard and radial water maze:relationship of hippocampal damage to performance[J].Behav-Brain-Res,1997,85(1):93-115.
[61]Zola Morgan S,Squire LR,Amaral DG.Human amnesia and medial temporal regulation:Enduring memory impairment following bilateral lesion limited to field CA1 of the hippocampus[J].Neurosci,1986,6:2950-2967.
[62]Ni J,Ohta H,Matsumoto K,et al.Progressive cognitive impairment following chronic cerebral hypoper-fusion induced by permanent occlusion of bilateral carotid arteries in rats[J].Brain-Res,1994;653(1-2):231-237.
[63]洪岸,姚志斌,顾耀明等.老年大鼠学习记忆减退与海马结构的突触素改变[J].解剖学报,1996,27(2):164-168.
[64]Janz R,Sudhof TC,Hammer RE,et al.Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I[J].Neuron,1999,24(3):687-700.
[65]Stroemer RP,Kent TA,Hulsebosch CE.Enhanced neuocortical neural sprouting,synaptogenesis,and behacioral recovery with D-amphetamine therapy after neocortical infarction in rats[J].Stroke,1998,29(11):2381-2393.
[66]Gottfries CG,Blennow K,Karlsson I,et al.The neurochemistry of vascular dementia[J].Dementia,1994,5(3-4):163-170.
[67]Tohgi H,Abe T,Kimura M,et al.Cerebospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia[J].J Neural Transm,1996,103(10):1211-1220.
[68]Oda Y.Choline acetyltransferase:the structure,distribution and pathologic changes in the central nervous system[J].Pathol Int,1999,49(11):921-937.
[69]苗建亭,游国雄,王者晋.血管性痴呆大鼠记忆障碍与海马胆碱能神经元关系的研究[J].中华老年医学杂志,1997,16(6):327-330.
[1]国家技术监督局.中华人民共和国国家标准·中医临床诊疗术语疾病部分.北京:中国标准出版社,1997.
[2]中华人民共和国卫生部.中药新药临床研究指导原则.中药新药治疗老年期痴呆的临床研究指导原则(草案),2000(内部资料).
[3]李正光,薛卫林,郭红梅.从破瘀化痰论治血管性痴呆理论分析[J].光明中医,2007, 22(8):19-21.
[4]张綦慧,张允岭,石玉如 等.无痴呆型血管性认知障碍的病因病机及证候学初步探讨[J].天津中医药,2005,22(1):49-52.
[5]陈刚,张六通,邱幸凡.血管性痴呆病机与治疗探讨[J].现代中西医结合杂志,2004,13(4):545-547.
[6]魏翠柏,田金洲,贾建平.老年痴呆中医病因病机理论的认识与思考[J].中华中医药杂志.2005,20(8):496-498.
[7]盛树力主编.老年性痴呆发病机理与药物研究.北京:科学技术文献出版社,2003:1-11.
[8]周文泉,于向东.关于血管性痴呆研究的思考.中医杂志,2002,42(4):9.
[9]陈忠义,李寅超.血管性痴呆之病位与病机分析[J].时珍国医国药,2007,18(6):1501-1502.
[10]张志真,刘慧林.血管性痴呆发病机制辨证论治的再认识与思考[J].北京中医,1999,8(5):9-12.
[11]武月萍,宫洪涛,张建刚等.论血管性痴呆与肾[J].中国中医急症,2003,12(1):45-46.
[12]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京:人民卫生出版社,2003:45.
[13]杨辰华,王永炎.血管性痴呆的中医病机及辨治思路[J].中医研究.2005,18(5):6-7.
[14]田金洲 等.血管性痴呆的诊断、辨证及疗效判定标准[J].北京中医药大学学报,2000,23(5):16-24.
[15]田金州,韩明向,涂晋文 等.血管性痴呆诊断、辨证及疗效评定标准(研究用).中国老年学杂志,2002,22(5):329-331.
[16]谢颖桢,高颖,邹忆怀 等.血管性痴呆分期辨证及综合治疗的探讨[J].北京中医药大学学报,2001,7(3):3-5.
[17]刘峘,田金洲,燕莉等.血管性痴呆患者证候学研究[J].北京中医药大学学报,2006,29(1):52-55.
[18]李宝丽.老年痴呆从肾虚论治机理探讨[J].山西中医,2006,22(2):1-3.
[19]郭海英.血管性痴呆中医治疗原则探讨[J].南京中医药大学学报.2005,21(4):221-222.
[20]孔令越,颜德馨.颜德馨教授以气血为纲辨证治疗血管性痴呆经验.四川中医,2005,23(8):4-5.
[21]李正光,薛卫林,郭红梅.从破瘀化痰论治血管性痴呆理论分析[J].光明中医,2007,22(8):19-21.
[22]曹金梅.化痰开窍法在血管性痴呆治疗中的重要作用[J].中医研究.2007.20(6):7-9.
[23]杨辰华,王永炎.血管性痴呆的中医病机及辨治思路[J].中医研究.2005,18(5):6-7.
[24]黄立武.血管性痴呆从肝论治初探[J].广西中医学院学报,2003,6(3):5-7.
[25]黄旖旎,何明大.脑灵汤对血管性痴呆大鼠行为学和血液流变学的影响[J].湖南中医药大学学报.2007,27(1):23-25.
[26]魏瑞,何明大,刘石梅.步长脑心通对血管性痴呆大鼠学习记忆及血管内皮细胞生长因子作用的影响[J].中风与神经疾病杂志.2006,2 3(3):306-308.
[27]徐祥清,朱丹,马世平.抑肝散对血管性痴呆大鼠学习记忆及脑组织SOD、MDA含量的影响[J].中国老年学杂志,2006.26(3):358-360..
[28]张力,王洪图.化呆醒神汤对大鼠血管性痴呆模型SS、SVP含量及SSmRNA表达的影响[J]. 中国中西医结合杂志,2001,21(8):608-610.
[29]王霞.白金丸对拟血管性痴呆小鼠脑病理组织学的影响[J].河北中医药学报,2005,20(1):6.
[30]薛卡明.清脑灵对拟血管性痴呆大鼠的作用[J].解放军医学杂志,2004,29(6):506.
[31]邓医宇,孙诚,曾红科等.银杏叶提取物对血管性痴呆大鼠海马胆碱能纤维的影响[J].中国临床康复,2004,8(25):5465-5468.
[32]朱崇霞.针刺百会、大椎对拟血管性痴呆大鼠GSH—PX、CAT的影响[J].上海针灸杂志,2004,2 3(3):40-41.
[33]王利春,刘海燕,王志勇等.针刺对拟血管性痴呆大鼠脑内NO、NOS及血液流变学影响的实验研究[J].针灸研究,2005,30(4):195-198.
[34]刘红健,秦鉴,陈文等.华佗再造丸治疗血管性痴呆的临床研究[J].中草药.2005,36(7):1052-1054.
[35]武宏.通窍活血汤加减治疗血管性痴呆40例[J].陕西中医.2006,27(11):1337-1338.
[36]邹蕴珏,吕宏义,程淑红.补阳还五汤加味治疗血管性痴呆30例临床报告[J].光明中医.2007,22(4):32-34.
[37]王万兴.陈宝贵治疗老年期脑血管性痴呆经验[J].中医杂志,2005,46(8):579-580.
[38]蔡晶 杜建 黄俊山 等.康欣胶囊对血管性痴呆影响的临床观察[J].中国老年学杂志.2003,23(8):482-484.
[39]黄俊山,林求诚,黄荣璋等.元通胶囊治疗血管性痴呆的临床研究[J].中国中西医结合杂志,2003,23(11):815-818.
[40]徐雯洁,李宗衡,史咏梅 等.颐神养脑胶囊治疗血管性痴呆的临床研究[J].中国中药杂志,2007,32(8):732-735.
[41]庄慧魁,迟永利,高志芳.化浊清脑合剂治疗血管性痴呆临床研究[J].山东中医药大学学报.2007,31(1):28-30.
[42]汤湘江,老膺荣,杨志敏等.补肾活血汤加减治疗血管性痴呆的临床研究[J].广州中医药大学学报.2005,22(6):426-429.
[43]沈双宏,杜建.补肾健脾养血活血方治疗血管性痴呆肾虚血瘀型的临床研究[J].湖南中医学院学报.2004,24(4):41-44.
[44]杨东东.补肾益智颗粒治疗轻中度血管性痴呆的有效性的临床研究[J].成都中医药大学学报.2006,29(2):6-7.
[45]郑万利,刘淑霞.黄连温胆汤配合针剌治疗血管性痴呆60例[J].陕西中医.2006,2 7(2):175-176
[2]柄澤昭秀.痴呆の疫学[J].治療,2004,86:11-15.
[3]Zhang ZX,Zahner GEP,Roman GC,et al.Dementia subtypes in China:prevalence in Beijing,Xian,Shanghai,and Chengdu[J].Arch Neurol,2005,62(3):447-453.
[4]朱飞奇,王正君,张海燕.王正君治疗血管性痴呆的临床经验[J].中国中医药信杂志,2004,11(2):169.
[5]赵宪林,方秀斌,李东培.大鼠血管性痴呆模型制作[J].中国医科大学学报,2002,31(3):166-168.
[6]林海,张壮,孙塑伦 等.拟血管性痴呆大鼠造模中应注意的几点问题[J].中医药学刊.2005,23(4):625-627.
[7]Morris R.Developments of a water-maze procedure for studying spatial learning in the rat[J].J Neurosci Methods,1984,11(1):47-60.
[8]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探[J].广州中医药大学学报[J],2000,17(2):117-119.
[9]李甘地 主编.组织病理技术[M].北京:人民卫生出版社,2002.
[10]田金洲,王永炎,刘峘 等.血管性痴呆发病机理研究[J].中医杂志,2003,44(8):565.
[11]赵勇,崔淑芳,汤球.血管性痴呆动物模型研究进展[J].上海实验动物科学,2005,25(1):54-58.
[12]de laTorre JC,Fortin T,Park GA et al.Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.Brain-Res,1992;582(2):186-195.
[13]Olsson Y,Brun A,Engiuund E.Fundamental pathological lesions in vascular dementia[J].Acta Neurol Scand Suppl,1996,168:31-38.
[14]李巍,张世仪。小鼠脑缺血性学习记忆障碍模型的建立[J].基础医学与临床,1995,15(6):46-49.
[15]刘汇波,叶翠飞,李斌 等.双侧颈总动脉结扎对大鼠学习记忆功能和海马组织形态学的影响[J],基础医学与临床,1998,18(4):54-58.
[16]Devan BD,Goad EH,Petri HL.Dissociation of hippocampal and striatal contributions to spatial navigation in the water maze.Neurobiol Learn Mem,1996,66(3):305-323.
[17]Tsuchiya M,Sako K,Yura S,et al.Local cerebral glucose utilization following acute and chronic bilateral carotid artery ligation in Wistar rats:relation to changes in local cerebral blood flow[J].Exp Brain Res,1993,95(1):1-8.
[18]Nanti M,Watanabe H.Availability of 2-V0 rats as a model for chronic cerebrovascular disease[J].Nippon Yakurigaku Zasshi,1999,113(2):85-95.
[19]Pappas BA,de la Torte JC,Davidson CM,el al.Chronic reduction blood flow in the adult rat:late-emerging CA1 cell loss and memory dysfunction[J].Brain Res,1996,708(1-2):50-58.
[20]Watanabe H,Ni HW,Sakai Y,et al.Permanent occlusion of bilateral internal carotid arteries produces cognitive deficits in two learning behavior tasks[J].Nihon Shinkei Seishin YakurigakuZasshi,1996,16(1):19-24.
[21]Myron D,Ginsberg N,Raul B.Rodent models of cerebral ischemia[J].Stroke,1989,20:1627-1642.
[22]Pulsinelli WA,Brierley JB.A new model of bilateral hemispheric ischemia in the unanesthetized rat[J].Stroke,1979,10(3):267-272.
[23]王蕊,杨秦飞,唐一鹏等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10):914-916.
[24]高东,周中和.实验性血管性痴呆的模型制作问题[J].国外医学·老年医学分册,2003,23(2):59-61.
[25]李巍,张世仪,赵惠敏 等.小鼠缺血性学习记忆障碍模型的建立[J].基础医学与临床,1995,15(6):46.
[26]唐启盛,黄启福,郭建文.高脂血症大鼠缺血再灌流诱发行为学障碍模型的实验研究[J].北京中医药大学学报,1997,20(5):34.
[27]王蕊,杨秦飞,庸鹏 等.大鼠拟“血管性痴呆”模型的改进[J].中国病理生理杂志,2000,16(10):914.
[28]林监,王子栋.血管性痴呆动物模型[J].中国应用生理学杂志,1998,14(1):89.
[29]梅建勋,张云岭,张伯礼 等.多发梗塞性痴呆人鼠模型的改进与应用[J].中国中西医结合杂志,2000,20(2):113.
[30]Takagi K,Takeo S.The model of stroke induced by microsphere embolism in rats[J].Nippon YakurigakuZasshi,2003,121(6):440-446.
[31]腾晶.康脑灵Ⅱ号治疗血管性痴呆实验与临床研究[J].山东中医药大学学报,2000,24(1):48.
[32]韩冬,廖福龙,李文 等.冷光源光化学诱导局灶性脑梗塞及血管损伤半暗带大鼠模型[J].中国微循环,2001,5(1):71.
[33]陈春富,郭述苏.大鼠局灶性脑缺血模型研究进展[J].国外医学·脑血管疾病分册,1995,3(5):227.
[34]Sabbatini M,Catalani A,Consoli C,et al.The hippocampus in spontaneously hypertensive rats:an animal model of vascular dementia[J].Mech Ageing Dev,2002,23(5):54-75.
[35]Saito H,Togashii H,Yoshioka M,et al.Animal model of vascular dementia with emphasis on stroke-prone spontaneously hypertension rats[J].Clin Exp Pharmacol Physiol,1995,22(1):257-266.
[36]陈惟昌,于萍,李占魁等.破坏海马角CA3区后小鼠记忆动力学变化[J].中日友好医院学报,1996,10(2):95.
[37]王浴生,邓文龙,薛春生.中药药理与应用[M].人民卫生出版社,北京,第二版,2000.
[38]张扩建.银杏叶治疗老年脑血管疾病临床研究[J].中成药.2005,27(9):1053-1055.
[39]吴海琴,张蓓,张桂莲 等.葛根素对脑缺血再灌注损伤的保护作用[J].卒中与神经疾病,2005,12(4):209-211.
[40]张冰清,王玉良.葛根素对血管性痴呆大鼠海马锥体细胞和BDNF表达的影响[J].神经解剖学杂志,2007,23(6):615-620.
[41]蒋晓燕,王晓雯,王雪飞 等.肉苁蓉总苷对大鼠局灶性脑缺血损伤的影响[J].中草药,2004,35(6):660-662.
[42]皋聪,王传社,巫冠中 等.苁蓉总甙对血管性痴呆大鼠学习记忆的影响及机制研究[J].中草药,2005,12(36):1852-1854.
[43]杨晋,陈随清,冀春茹 等.山茱萸化学成分的分离鉴定[J].中草药,2005,36(12):1780-1782.
[44]藏连碧,郑怡建.山茱萸抗衰老实验研究[J].浙江中医学院学报,1993,17(5):34.
[45]苗明三,杨云.山茱萸多糖抗氧化作用研究[J].河南中医,2002,22(1):66-67.
[46]沈映君 主编.中药药理学.上海:上海科学技术出版社.1997.
[47]郭长杰,伍杰雄,李若馨.三七总皂苷对痴呆模型大鼠大脑皮质内神经递质含量的影响[J].中国临床药学杂志.2004,13(3):150-152.
[48]钟振国,屈泽强,王乃平 等.三七总皂苷对大脑基底核损伤动物模型大脑神经元突触素的影响[J].中国中药杂志,2005,30(12):913-915.
[49]卢家红,吕传真,洪震 等.尼麦角林治疗血管性痴呆的前瞻性、双盲、多中心研究[J].中华神经科杂志,2001,34(2):88-91.
[50]叶莉英,翟金霞,高建国.尼麦角林治疗脑血管病伴记忆功能障碍50例疗效观察[J].临床神经病学杂志,2004,17(2):142-143.
[51]Morris R GM,Garrud P,Rawlins J NP,et al.Place nayigation impaired in rats with hippocampallesions[J].Nature,1982,297:681-684.
[52]关新民.医学神经生物学纲要[M].北京:科学出版社.2003.
[53]胡镜清,温泽淮,赖世隆.Morris水迷宫检测的记忆属性与方法学初探.广州中医药大学学报,2000,17(2):117-119.
[54]Gandhi CC,Kellyl RM,Wiley RG,et al.Impaired acquisition of a Morris water maze task following selective destruction of cerebellar Purkinje cells with 0X7-saporin.Behav Brain Res,2000;109(1):37-47.
[55]韩太真,吴馥梅.学习与记忆的神经生物学[M].北京:北京医科大学、中国协和医科大学联合出版社,1998,162-177.
[56]Kirino.Delayed neuronal death in the gerbil hippocampus following ischemia[J].Brain Res,1982,239:57-69.
[57]de-la-Torre,JC;Fortin,T;Park,GA;et al.Brain blood flow restoration rescues chronically damaged rat CA1 neurons[J].Brain-Res,1993:623(1):6-15.
[58]Akhondzadeh S.Hippocampal synaptic plasticity and cognition[J].J Clin Pharmacol Ther,1999;24(4):241-249.
[59]Whishaw IQ,Rod MR,Auer RN.Behavioral deficits revealed by multiple tests in rats with ischemic damage limited to half of the CA1 sector of the hippocampus[J].Brain Res Bull.1994;34(3):283-292.
[60]Nelson A,Lebessih,Sowinski P,et al.Comparison of effects global cerebral ischemia on spatial learning in the standard and radial water maze:relationship of hippocampal damage to performance[J].Behav-Brain-Res,1997,85(1):93-115.
[61]Zola Morgan S,Squire LR,Amaral DG.Human amnesia and medial temporal regulation:Enduring memory impairment following bilateral lesion limited to field CA1 of the hippocampus[J].Neurosci,1986,6:2950-2967.
[62]Ni J,Ohta H,Matsumoto K,et al.Progressive cognitive impairment following chronic cerebral hypoper-fusion induced by permanent occlusion of bilateral carotid arteries in rats[J].Brain-Res,1994;653(1-2):231-237.
[63]洪岸,姚志斌,顾耀明等.老年大鼠学习记忆减退与海马结构的突触素改变[J].解剖学报,1996,27(2):164-168.
[64]Janz R,Sudhof TC,Hammer RE,et al.Essential roles in synaptic plasticity for synaptogyrin I and synaptophysin I[J].Neuron,1999,24(3):687-700.
[65]Stroemer RP,Kent TA,Hulsebosch CE.Enhanced neuocortical neural sprouting,synaptogenesis,and behacioral recovery with D-amphetamine therapy after neocortical infarction in rats[J].Stroke,1998,29(11):2381-2393.
[66]Gottfries CG,Blennow K,Karlsson I,et al.The neurochemistry of vascular dementia[J].Dementia,1994,5(3-4):163-170.
[67]Tohgi H,Abe T,Kimura M,et al.Cerebospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia[J].J Neural Transm,1996,103(10):1211-1220.
[68]Oda Y.Choline acetyltransferase:the structure,distribution and pathologic changes in the central nervous system[J].Pathol Int,1999,49(11):921-937.
[69]苗建亭,游国雄,王者晋.血管性痴呆大鼠记忆障碍与海马胆碱能神经元关系的研究[J].中华老年医学杂志,1997,16(6):327-330.
[1]国家技术监督局.中华人民共和国国家标准·中医临床诊疗术语疾病部分.北京:中国标准出版社,1997.
[2]中华人民共和国卫生部.中药新药临床研究指导原则.中药新药治疗老年期痴呆的临床研究指导原则(草案),2000(内部资料).
[3]李正光,薛卫林,郭红梅.从破瘀化痰论治血管性痴呆理论分析[J].光明中医,2007, 22(8):19-21.
[4]张綦慧,张允岭,石玉如 等.无痴呆型血管性认知障碍的病因病机及证候学初步探讨[J].天津中医药,2005,22(1):49-52.
[5]陈刚,张六通,邱幸凡.血管性痴呆病机与治疗探讨[J].现代中西医结合杂志,2004,13(4):545-547.
[6]魏翠柏,田金洲,贾建平.老年痴呆中医病因病机理论的认识与思考[J].中华中医药杂志.2005,20(8):496-498.
[7]盛树力主编.老年性痴呆发病机理与药物研究.北京:科学技术文献出版社,2003:1-11.
[8]周文泉,于向东.关于血管性痴呆研究的思考.中医杂志,2002,42(4):9.
[9]陈忠义,李寅超.血管性痴呆之病位与病机分析[J].时珍国医国药,2007,18(6):1501-1502.
[10]张志真,刘慧林.血管性痴呆发病机制辨证论治的再认识与思考[J].北京中医,1999,8(5):9-12.
[11]武月萍,宫洪涛,张建刚等.论血管性痴呆与肾[J].中国中医急症,2003,12(1):45-46.
[12]王永炎,张伯礼.血管性痴呆现代中医临床与研究[M].北京:人民卫生出版社,2003:45.
[13]杨辰华,王永炎.血管性痴呆的中医病机及辨治思路[J].中医研究.2005,18(5):6-7.
[14]田金洲 等.血管性痴呆的诊断、辨证及疗效判定标准[J].北京中医药大学学报,2000,23(5):16-24.
[15]田金州,韩明向,涂晋文 等.血管性痴呆诊断、辨证及疗效评定标准(研究用).中国老年学杂志,2002,22(5):329-331.
[16]谢颖桢,高颖,邹忆怀 等.血管性痴呆分期辨证及综合治疗的探讨[J].北京中医药大学学报,2001,7(3):3-5.
[17]刘峘,田金洲,燕莉等.血管性痴呆患者证候学研究[J].北京中医药大学学报,2006,29(1):52-55.
[18]李宝丽.老年痴呆从肾虚论治机理探讨[J].山西中医,2006,22(2):1-3.
[19]郭海英.血管性痴呆中医治疗原则探讨[J].南京中医药大学学报.2005,21(4):221-222.
[20]孔令越,颜德馨.颜德馨教授以气血为纲辨证治疗血管性痴呆经验.四川中医,2005,23(8):4-5.
[21]李正光,薛卫林,郭红梅.从破瘀化痰论治血管性痴呆理论分析[J].光明中医,2007,22(8):19-21.
[22]曹金梅.化痰开窍法在血管性痴呆治疗中的重要作用[J].中医研究.2007.20(6):7-9.
[23]杨辰华,王永炎.血管性痴呆的中医病机及辨治思路[J].中医研究.2005,18(5):6-7.
[24]黄立武.血管性痴呆从肝论治初探[J].广西中医学院学报,2003,6(3):5-7.
[25]黄旖旎,何明大.脑灵汤对血管性痴呆大鼠行为学和血液流变学的影响[J].湖南中医药大学学报.2007,27(1):23-25.
[26]魏瑞,何明大,刘石梅.步长脑心通对血管性痴呆大鼠学习记忆及血管内皮细胞生长因子作用的影响[J].中风与神经疾病杂志.2006,2 3(3):306-308.
[27]徐祥清,朱丹,马世平.抑肝散对血管性痴呆大鼠学习记忆及脑组织SOD、MDA含量的影响[J].中国老年学杂志,2006.26(3):358-360..
[28]张力,王洪图.化呆醒神汤对大鼠血管性痴呆模型SS、SVP含量及SSmRNA表达的影响[J]. 中国中西医结合杂志,2001,21(8):608-610.
[29]王霞.白金丸对拟血管性痴呆小鼠脑病理组织学的影响[J].河北中医药学报,2005,20(1):6.
[30]薛卡明.清脑灵对拟血管性痴呆大鼠的作用[J].解放军医学杂志,2004,29(6):506.
[31]邓医宇,孙诚,曾红科等.银杏叶提取物对血管性痴呆大鼠海马胆碱能纤维的影响[J].中国临床康复,2004,8(25):5465-5468.
[32]朱崇霞.针刺百会、大椎对拟血管性痴呆大鼠GSH—PX、CAT的影响[J].上海针灸杂志,2004,2 3(3):40-41.
[33]王利春,刘海燕,王志勇等.针刺对拟血管性痴呆大鼠脑内NO、NOS及血液流变学影响的实验研究[J].针灸研究,2005,30(4):195-198.
[34]刘红健,秦鉴,陈文等.华佗再造丸治疗血管性痴呆的临床研究[J].中草药.2005,36(7):1052-1054.
[35]武宏.通窍活血汤加减治疗血管性痴呆40例[J].陕西中医.2006,27(11):1337-1338.
[36]邹蕴珏,吕宏义,程淑红.补阳还五汤加味治疗血管性痴呆30例临床报告[J].光明中医.2007,22(4):32-34.
[37]王万兴.陈宝贵治疗老年期脑血管性痴呆经验[J].中医杂志,2005,46(8):579-580.
[38]蔡晶 杜建 黄俊山 等.康欣胶囊对血管性痴呆影响的临床观察[J].中国老年学杂志.2003,23(8):482-484.
[39]黄俊山,林求诚,黄荣璋等.元通胶囊治疗血管性痴呆的临床研究[J].中国中西医结合杂志,2003,23(11):815-818.
[40]徐雯洁,李宗衡,史咏梅 等.颐神养脑胶囊治疗血管性痴呆的临床研究[J].中国中药杂志,2007,32(8):732-735.
[41]庄慧魁,迟永利,高志芳.化浊清脑合剂治疗血管性痴呆临床研究[J].山东中医药大学学报.2007,31(1):28-30.
[42]汤湘江,老膺荣,杨志敏等.补肾活血汤加减治疗血管性痴呆的临床研究[J].广州中医药大学学报.2005,22(6):426-429.
[43]沈双宏,杜建.补肾健脾养血活血方治疗血管性痴呆肾虚血瘀型的临床研究[J].湖南中医学院学报.2004,24(4):41-44.
[44]杨东东.补肾益智颗粒治疗轻中度血管性痴呆的有效性的临床研究[J].成都中医药大学学报.2006,29(2):6-7.
[45]郑万利,刘淑霞.黄连温胆汤配合针剌治疗血管性痴呆60例[J].陕西中医.2006,2 7(2):175-176