参附对局灶性脑缺血及颅脑手术损伤保护作用的研究
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摘要
脑缺血性疾病常可导致不同程度的神经功能障碍，严重影响患者生活质量，甚至危及生命，给患者及其家庭带来了痛苦，增加了社会负担。近年来，随着对脑缺血性损伤病理生理机制的深入研究，发现了许多新的脑保护措施及药物，然而在实际的临床治疗中并未取得良好的疗效。参附注射液作为一种中药复方制剂，在脑缺血性损伤中的保护作用已被动物实验证实，但对其脑保护作用机制及临床治疗效果报道较少。本文旨在以局灶性脑缺血模型及颅脑手术病人为研究对象，探讨参附注射液脑保护作用及其部分机制。
实验一：目的 研究参附注射液对大鼠短暂性局灶性脑缺血再灌注损伤HSP70和HSP90表达的影响。方法 30只雄性SD大鼠，随机分为三组(每组n=10)：假手术组(Sham组)；单纯缺血再灌注组(MCAO组)；保护组(SF组)，分别在缺血前30min经腹腔注射生理盐水或参附注射液10ml·kg~(-1)。采用颈内动脉尼龙线线栓法致右侧大脑中动脉栓塞(120min)模型，观察再灌注后24h时脑组织HSP70和HSP90的表达及病理学改变。结果 再灌注24h后SF组组织病理学损害轻于MCAO组。免疫组化结果显示假手术组HSP70及HSP90均未见表达；MCAO组可见到较多的HSP70
第四军医夕气学硕士学位论文
免疫阳性细胞(0 .73士0.68)，与假手术组有明显差别(P<0.05);sF
组HsP70免疫阳性细胞(2 .02士0.86)分布较McAO组广泛，数量
明显增多，胞浆及胞核都可见HSP7O的表达，与MCAO组有明
显差别(p<0.05)，而SF组HSpgo(0.13士0.15)的表达与MCAO组
(0 .14士0.12)比较无明显变化(P>0.05)。结论参附注射液可增加脑
缺血再灌注损伤后HSP7O的表达，但对HSPgO的表达无明显影
响。
实验二:目的观察参附注射液对颅脑手术病人血清SOD活
性和MDA含量的影响。方法40例ASAI一H级幕上肿瘤行择期
开颅手术的病人，随机分为两组:I组(n二20)，生理盐水对照组;
11组(n=20)SF组。11组于切开硬脑膜后，用0.9%生理盐水将50ml
参附注射液稀释至200ml，输注时间为20min;I组于同一时间
点输入0.9%生理盐水200ml作为对照。分别于输注前(BI)、输注
后即刻(Al)及输注后60min(AI60)三个时间点，采集颈内静脉球部
血样，检测血清中超氧化物歧化酶(S OD)和丙二醛(MDA)的活性
和含量，并记录对应时间点的心率(HR)、平均动脉压(MAP)。结
果对照组(I组)MDA含量于输注后60min(AI60)明显升高，与输
注前(BI)比较有显著性差异(P<0.05)，与输注后即刻(Al)比较则无
明显变化(P>.05)，输注前(BI)及输注后即刻(Al)的MDA含量无
明显变化(p>0.05);sF组(11组)MDA含量在输注前(BI)、输注后
即刻(Al)及输注后60min(AI60)三个时间点无明显变化(P>0.05)。
对照组(I组)S oD活性在输注前(Bl)、输注后即刻(Al)及输注后
6omin(Ax6o)三个时间点均无明显变化护>0.05);sF组(11组)soD
活性于输注后6Omin(AI60)明显升高，与输注前(BI)比较有显著性
差异(P<0.仍)，与输注后即刻(AD比较则无明显变化(P>.05)，输
注前(BD及输注后即刻(Al)的s0D活性无明显差异(P>0.05)。组
间比较:输注后6Omin时的MDA含量对照组明显高于SF组
(P<0.05)，sOD活性SF组明显高于对照组(P<0.05)。结论在颅
第四军医大学不页士学位论文
脑手术围术期应用SF可提高脑内SOD活性，降低MDA含量，
具有清除氧自由基、抗氧化损伤的作用。
实验三:目的观察参附注射液对颅脑手术病人康复效果的
影响。方法200例ASAI一H级颅内肿瘤行择期开颅手术的病人，
随机分为两组:I组(n二100)，生理盐水对照组;11组(n二100)，
SF组。麻醉稳定后，11组即用0.9%生理盐水将50ml参附注射液
稀释至200ml，输注时间为20min;I组于同一时间点输入0.9%
生理盐水200ml作为对照。分别记录术毕清醒时间、拔管时间、
住神经外科监护室(NICU)天数、住院天数，并采用Karnofsky
评分量表分别在术前及出院时对病人的生存质量作出评估。结果
两组病人的苏醒时间、拔管时间及住NICU天数无明显差别
(P>0 .05)，而SF组的住院天数(25士7.65)较对照组(27士7.37)减少
(P<0.05)，两组病人出院时的评分均较术前明显降低(P<0.05)，但
两组间无明显差异(P>.05)。结论在颅脑手术围术期给予参附注
射液能够缩短平均住院日，但对出院时病人的生存质量无明显改
盖
实验四:目的观察参附注射液对颅脑手术病人脑氧供需平
衡的影响。方法30例ASAI一H级幕上肿瘤行择期开颅手术的病
人，随机分为两组;I组(n=15)，生理盐水对照组;H组(n=15)，
SF组。术中切开硬脑膜后，11组即用0.9%生理盐水将50ml参附
注射液稀释至200ml于20min内静脉输入;I组在同一时间给予
0.9%生理盐水200ml。分别于输注前(BI)、输注完即刻(AI)及输注
后30min(AI30)三个时间点，同步采集颈静脉球和足背动脉血行
血气分析，并计算动脉、颈静脉球血氧含量(CaOZ、CjvOZ)、动-
颈内静脉血氧含量差(Ca一vOZ)及脑氧摄取率(C ERoZ);结果输
注sF前后两组间HR和MAP无明显变化(p>0.05);SjvOZ，PjvOZ，
caoZ，ca-jvo:及cERo:等指标在SF输注前、后均无明显变化，
两组间亦无显著性差异(P>0.05)。结论在神经外科手术围术期
第四军医大学不页d匕学t立论文
给予参附注射液对脑的氧供需平
Background Ischemic cerebrovascular disease often leads to neurologic deficits which seriously influence the quality of life and even threaten the survival of patients. Recently, a number of measures and drugs have been proved to protect neurons from ischemia-reperfusion damage. However, there is no effective therapeutic drug in clinic practice. Shenfu injection, a traditional Chinese medicine, was proved to have protective effects on cerebral ischemia-reperfusion injury in rats. But its mechanism and therapeutic efficacy in clinical patients are still unclear. The present study was designed to disclose the mechanism of neuroprotection induced by Shenfu injection and evaluate the therapeutic efficacy in clinical patients.
Experiment 1. Objective: To investigate the effects of Shenfu injection (SF) on the expression of HSP70 and HSP90 after cerebral ischemia-reperfusion in rats. Methods: Thirty male Sprague-Dawley (SD) rats weighing 280~320g were randomized into three groups (n=10 in each group): sham-operated group; MCAO group and SF group . The rats in SF group received intraperitoneal injection of SF 10ml kg-1 at 30 min before 120min MCAO. The
pathological outcome and the expression of HSP70 and HSP90 were evaluated at 24h post reperfusion. Results: The pathological outcome of SF group was better than that of MCAO group. The expression of HSP70, HSP90 was negative in sham-operated group. The expression of HSP70 in SF group was significantly stronger than that of MCAO group at 24h after reperfusion, but the expression of HSP90 in SF group presented no difference to that in MCAO group. Conclusion: Transient focal cerebral ischemia induced the expression of HSP70. Administration of SF before cerebral ischemia could increase the expression of HSP70, but HSP90 protein levels remained constant.
Experiment 2. Objective: To investigate the effect of Shenfu injection (SF) on the superoxide dismutase activities (SOD) and malondialdehyde (MDA) levels in patient undergoing craniotomy. Methods: Fourty ASA grade I -II patients undergoing elective craniotomy for supratentorial cerebral tumor removal were included in a randomized study consisting of 2 groups: Patients in group II (SF group, n=20) received SF 50ml diluted with 0.9% NaCl 150ml within 20 minutes after opening the dura. Blood samples were taken from internal jugular venous bulb for measuring SOD activities and MDA levels before infusion (BI), after infusion (AI) and 60 min after infusion (AI60), respectively, and Heart rate (HR), Mean arterial pressure (MAP) were recorded. While patients in group I (control, n=20) received 0.9% NaCl 200 ml at the same time. Results: Compared with BI, MDA levels were significant increased at AI60 (P<0.05), but no significant difference was found between BI and AI in group I (P>0.05). In group II , there was no significant difference in MDA levels among BI, AI and AI60 (P>0.05).
Compared with BI, SOD activities significantly increased at AI60 (P<0.05), but no significant difference was found between BI and AI in group II(P>0.05). No significant difference was found among BI, AI, and AI60 in group I (P>0.05). Sixty minutes after infusion, MDA levels in group II were significantly lower (P<0.05), and SOD activities in group II were significantly higher (P<0.05) than that in group I , respectively. Conclusion: Infusion of SF attenuates the formation of free radicals in patients undergoing craniotomy .
Experiment 3. Objective: To investigate the effect of Shenfu injection (SF) on the recovery in patient undergoing craniotomy. Methods: Two hundred ASA grade I - II patients undergoing elective craniotomy for cerebral tumor removal were included in a randomized study consisting of 2 groups: Patients in group II (SF group, n=100) received SF 50ml diluted with 0.9% NaCl 150ml within 20 minutes after anesthesia .While group I as control group (control, n=100) received 0.9% NaCl 200 ml at the same time. Awakening time from anesthesia (Awak), time of extubation (Extu), length of stay in neurosurgical intensive care unit (NICU), le
实验一：目的 研究参附注射液对大鼠短暂性局灶性脑缺血再灌注损伤HSP70和HSP90表达的影响。方法 30只雄性SD大鼠，随机分为三组(每组n=10)：假手术组(Sham组)；单纯缺血再灌注组(MCAO组)；保护组(SF组)，分别在缺血前30min经腹腔注射生理盐水或参附注射液10ml·kg~(-1)。采用颈内动脉尼龙线线栓法致右侧大脑中动脉栓塞(120min)模型，观察再灌注后24h时脑组织HSP70和HSP90的表达及病理学改变。结果 再灌注24h后SF组组织病理学损害轻于MCAO组。免疫组化结果显示假手术组HSP70及HSP90均未见表达；MCAO组可见到较多的HSP70
第四军医夕气学硕士学位论文
免疫阳性细胞(0 .73士0.68)，与假手术组有明显差别(P<0.05);sF
组HsP70免疫阳性细胞(2 .02士0.86)分布较McAO组广泛，数量
明显增多，胞浆及胞核都可见HSP7O的表达，与MCAO组有明
显差别(p<0.05)，而SF组HSpgo(0.13士0.15)的表达与MCAO组
(0 .14士0.12)比较无明显变化(P>0.05)。结论参附注射液可增加脑
缺血再灌注损伤后HSP7O的表达，但对HSPgO的表达无明显影
响。
实验二:目的观察参附注射液对颅脑手术病人血清SOD活
性和MDA含量的影响。方法40例ASAI一H级幕上肿瘤行择期
开颅手术的病人，随机分为两组:I组(n二20)，生理盐水对照组;
11组(n=20)SF组。11组于切开硬脑膜后，用0.9%生理盐水将50ml
参附注射液稀释至200ml，输注时间为20min;I组于同一时间
点输入0.9%生理盐水200ml作为对照。分别于输注前(BI)、输注
后即刻(Al)及输注后60min(AI60)三个时间点，采集颈内静脉球部
血样，检测血清中超氧化物歧化酶(S OD)和丙二醛(MDA)的活性
和含量，并记录对应时间点的心率(HR)、平均动脉压(MAP)。结
果对照组(I组)MDA含量于输注后60min(AI60)明显升高，与输
注前(BI)比较有显著性差异(P<0.05)，与输注后即刻(Al)比较则无
明显变化(P>.05)，输注前(BI)及输注后即刻(Al)的MDA含量无
明显变化(p>0.05);sF组(11组)MDA含量在输注前(BI)、输注后
即刻(Al)及输注后60min(AI60)三个时间点无明显变化(P>0.05)。
对照组(I组)S oD活性在输注前(Bl)、输注后即刻(Al)及输注后
6omin(Ax6o)三个时间点均无明显变化护>0.05);sF组(11组)soD
活性于输注后6Omin(AI60)明显升高，与输注前(BI)比较有显著性
差异(P<0.仍)，与输注后即刻(AD比较则无明显变化(P>.05)，输
注前(BD及输注后即刻(Al)的s0D活性无明显差异(P>0.05)。组
间比较:输注后6Omin时的MDA含量对照组明显高于SF组
(P<0.05)，sOD活性SF组明显高于对照组(P<0.05)。结论在颅
第四军医大学不页士学位论文
脑手术围术期应用SF可提高脑内SOD活性，降低MDA含量，
具有清除氧自由基、抗氧化损伤的作用。
实验三:目的观察参附注射液对颅脑手术病人康复效果的
影响。方法200例ASAI一H级颅内肿瘤行择期开颅手术的病人，
随机分为两组:I组(n二100)，生理盐水对照组;11组(n二100)，
SF组。麻醉稳定后，11组即用0.9%生理盐水将50ml参附注射液
稀释至200ml，输注时间为20min;I组于同一时间点输入0.9%
生理盐水200ml作为对照。分别记录术毕清醒时间、拔管时间、
住神经外科监护室(NICU)天数、住院天数，并采用Karnofsky
评分量表分别在术前及出院时对病人的生存质量作出评估。结果
两组病人的苏醒时间、拔管时间及住NICU天数无明显差别
(P>0 .05)，而SF组的住院天数(25士7.65)较对照组(27士7.37)减少
(P<0.05)，两组病人出院时的评分均较术前明显降低(P<0.05)，但
两组间无明显差异(P>.05)。结论在颅脑手术围术期给予参附注
射液能够缩短平均住院日，但对出院时病人的生存质量无明显改
盖
实验四:目的观察参附注射液对颅脑手术病人脑氧供需平
衡的影响。方法30例ASAI一H级幕上肿瘤行择期开颅手术的病
人，随机分为两组;I组(n=15)，生理盐水对照组;H组(n=15)，
SF组。术中切开硬脑膜后，11组即用0.9%生理盐水将50ml参附
注射液稀释至200ml于20min内静脉输入;I组在同一时间给予
0.9%生理盐水200ml。分别于输注前(BI)、输注完即刻(AI)及输注
后30min(AI30)三个时间点，同步采集颈静脉球和足背动脉血行
血气分析，并计算动脉、颈静脉球血氧含量(CaOZ、CjvOZ)、动-
颈内静脉血氧含量差(Ca一vOZ)及脑氧摄取率(C ERoZ);结果输
注sF前后两组间HR和MAP无明显变化(p>0.05);SjvOZ，PjvOZ，
caoZ，ca-jvo:及cERo:等指标在SF输注前、后均无明显变化，
两组间亦无显著性差异(P>0.05)。结论在神经外科手术围术期
第四军医大学不页d匕学t立论文
给予参附注射液对脑的氧供需平
Background Ischemic cerebrovascular disease often leads to neurologic deficits which seriously influence the quality of life and even threaten the survival of patients. Recently, a number of measures and drugs have been proved to protect neurons from ischemia-reperfusion damage. However, there is no effective therapeutic drug in clinic practice. Shenfu injection, a traditional Chinese medicine, was proved to have protective effects on cerebral ischemia-reperfusion injury in rats. But its mechanism and therapeutic efficacy in clinical patients are still unclear. The present study was designed to disclose the mechanism of neuroprotection induced by Shenfu injection and evaluate the therapeutic efficacy in clinical patients.
Experiment 1. Objective: To investigate the effects of Shenfu injection (SF) on the expression of HSP70 and HSP90 after cerebral ischemia-reperfusion in rats. Methods: Thirty male Sprague-Dawley (SD) rats weighing 280~320g were randomized into three groups (n=10 in each group): sham-operated group; MCAO group and SF group . The rats in SF group received intraperitoneal injection of SF 10ml kg-1 at 30 min before 120min MCAO. The
pathological outcome and the expression of HSP70 and HSP90 were evaluated at 24h post reperfusion. Results: The pathological outcome of SF group was better than that of MCAO group. The expression of HSP70, HSP90 was negative in sham-operated group. The expression of HSP70 in SF group was significantly stronger than that of MCAO group at 24h after reperfusion, but the expression of HSP90 in SF group presented no difference to that in MCAO group. Conclusion: Transient focal cerebral ischemia induced the expression of HSP70. Administration of SF before cerebral ischemia could increase the expression of HSP70, but HSP90 protein levels remained constant.
Experiment 2. Objective: To investigate the effect of Shenfu injection (SF) on the superoxide dismutase activities (SOD) and malondialdehyde (MDA) levels in patient undergoing craniotomy. Methods: Fourty ASA grade I -II patients undergoing elective craniotomy for supratentorial cerebral tumor removal were included in a randomized study consisting of 2 groups: Patients in group II (SF group, n=20) received SF 50ml diluted with 0.9% NaCl 150ml within 20 minutes after opening the dura. Blood samples were taken from internal jugular venous bulb for measuring SOD activities and MDA levels before infusion (BI), after infusion (AI) and 60 min after infusion (AI60), respectively, and Heart rate (HR), Mean arterial pressure (MAP) were recorded. While patients in group I (control, n=20) received 0.9% NaCl 200 ml at the same time. Results: Compared with BI, MDA levels were significant increased at AI60 (P<0.05), but no significant difference was found between BI and AI in group I (P>0.05). In group II , there was no significant difference in MDA levels among BI, AI and AI60 (P>0.05).
Compared with BI, SOD activities significantly increased at AI60 (P<0.05), but no significant difference was found between BI and AI in group II(P>0.05). No significant difference was found among BI, AI, and AI60 in group I (P>0.05). Sixty minutes after infusion, MDA levels in group II were significantly lower (P<0.05), and SOD activities in group II were significantly higher (P<0.05) than that in group I , respectively. Conclusion: Infusion of SF attenuates the formation of free radicals in patients undergoing craniotomy .
Experiment 3. Objective: To investigate the effect of Shenfu injection (SF) on the recovery in patient undergoing craniotomy. Methods: Two hundred ASA grade I - II patients undergoing elective craniotomy for cerebral tumor removal were included in a randomized study consisting of 2 groups: Patients in group II (SF group, n=100) received SF 50ml diluted with 0.9% NaCl 150ml within 20 minutes after anesthesia .While group I as control group (control, n=100) received 0.9% NaCl 200 ml at the same time. Awakening time from anesthesia (Awak), time of extubation (Extu), length of stay in neurosurgical intensive care unit (NICU), le
引文
1. Abe K, Tanzi RE, Kogure K. Induction of HSP70 mRNA after tranisent ischemia in gerbil brain. Neurosci Lett, 1991;125:166-168
2. Andrews PJD, Dearden NM, Miller JD. Jugular bulb cannulation technique validation of a new continuous monitor. Br J Anaesth, 1991;67:533-558
3. Andrews RJ, Bringas JR A. review of srain retpaction and recommendations for minimizing intraoperative brain injury. Neurosurgery, 1993;33: 1052
4. Aoke M, Age K, Kavague J, et al. The preconditioned hippocampus accelerates HSP70 heat shock gene expression following transient ischemia in gerbils. Neurosci Lett, 1993,155(1):7-10
5. Aronowski J, Grotta JC, Waxham MN, et al. Ischemia-induced translocation of Ca~(2+)/calmodulin-dependent protein kinase Ⅱ: potential role in neuronal damage. Neurochem, 1992,58(5): 1743
6. Attle AS, Wu JA, Yuan CS. Ginseng pharmacology: Multiple constituents and multiple actions. Biochem Pharmacol, 1999,58:1685-1693
7. Barber DA, Hamis SR. Oxygen free radical and antioxidants: A review. Am Pham, 1994,34(9):26-35
8. Baron JC. Mapping the ischemic penumbra with PET:implications for acute stroke treatment. Cerebrovasc Dis, 1999, 9(4):193-201
9. Chan PH. Role of oxidants in ischemia brain damage. Stroke, 1996; 27:1124-1129.
10. Chen J, Graham SH, Zhu RL, et al. Stress proteins and tolerance
to focal cerebral ischemia. J Cereb Blood Flow Metab 1996,16(3):566-577.
11. Chen SY, Wang Q, Zeng XL, et al. The effect of PaCO_2 on the balance of cerebral oxygen supply and consumption during intravenous gerneral anesthesia. J Med Coll PLA,1999;14(4):274-277.
12. Collard CD, Vakeva A, Morrissey MA, et al. Complement activation after oxidative stresss: role of the lectin complement pathway. Am J Pathol, 2000,156(5): 1549-1556.
13. Coyle JT, Puttfarcken P. Oxidative stresss, glutamate, and the neurodegenerative discorders. Science, 1993,262:689
14. Cruz J, Jaggi JT, Hoffstad OJ. Cerebral blood flow and oxygen consumption in acute brain injury with acute anemia: an alternative for the cerebral metabolic rate of oxygen consumption? Crit Care Med,1993,21:1218-1214
15. De Jesus O, Sekhar LN, Parikh HK, et al. Long-term follow up of patients with meningiomas involving the cavernous sinus: Recurrence, progression, and quality of life. Neurosurgery, 1996,39:915-920.
16. Facob RA, Burri BJ. Oxidative damage and defence. Am J Clin Nutr, 1996,63(6):9805-9853.
17. Fisher M, Schaebitz W. An overview of acute stroke therapy: past, present, and future. Arch Intern Med 2000; 160(21): 3196-3206.
18. Fourie AM, Hupp YR, Lane DP. HSP70 binding sites in the tumor suppressor protein P53. J Biol Chem,1997;272(40): 19471-19479.
19. Gastagne V, Gautschi M, Lefevre K, et al. Relationshiop between neuronal death and cellullar redos status. Focus on the
developing nervous system. Prog Neurobiol, 1999, 59:397-423.
20. Higashi T, Takechi H., Uemura Y, et al. Differential induction of mRNA species encoding several classes of stress proteins following focal cerebral ischemia in rats, Brain Res, 1994,650:239-248
21. Huang KC. The pharmacology of Chinese herbs. CRC Press, Boca Raton, FL, 1999
22. Hutchison, KA, Dittmar, KD Pratt, WB. All of the factors required for assembly of the glucocorticoid receptor into a functional heterocomplex with heat shock protein 90 are preassociated in a self-sufficient protein folding structure, a foldosome, J Biol Chem., 1994,269:27894-27899
23. Jarskog LF, Gilmore JH. Developmental expression of Bel-2 protein in human cotex. Brain Res Dev Brain Res, 2000,119: 225-230
24. Jiang XY, Zhang JT, Shi CZ. Mechanism of action of ginsenoside Rb_1 in decreasing intracellular Ca~(2+). Acta Pharm Sin, 1996,31:321-326
25. Jonathan W, Graham M. Management of severe head injury, Contemporary Neurosurgery, 1996,18:1～5
26. Kader A, Frazzini VI, Solomon RA, et al. Nitric Oxide production during cerebral ischemia in rats. Stroke, 1993,24:1709
27. Kato H, Kanellopoulos GK, Matsuo S, et al. Neuronal apoptosiss and necrosis following spinal cord ischemia in the rat. Exp Neurol, 1998, 148(2):464-474
28. Kawagoe J, Abe K., Aoki M et al. Induction of HSP90 (?)heat shock mRNA after transient global ischemia in gerbil hippocampus, Brain Res, 1993, 621:121-125
29. Kim CS, Park JB, Kim KJ, et al. Effect of Korea red ginseng on cerebral blood flow and superoxide production. Acta Pharmacol Sin, 2002;23(12): 1152-1156
30. Kinouch H, Sharp FR, Hill MP, et al. Induction of 70-kDa heat shock protein and HSP70 mRNA following transient focal cerebral ischemia in the rat. Cereb Blood Metab, 1993; 13(1): 105-115
31. Kinuta Y, Kinmura M, Tokawa Y, et al. Change in xanthine oxidase in ischemic rat brain. J Neurosurg, 1989,71 (3):417
32. Lim JH, Wen TC, Metsuda s, et al. Protection of ischemic hippocampal neurons by ginsenoside Rb_1, a main ingredient of ginseng root. Neurosci Res 1997; 28:191-200
33. Marcus JD, Yolanda CM, Benjamin SA, et al. Focal cerebral ischemia increase the levels of several classes of heat shock proteins and their corresponding mRNAs. Molecular Brain Research, 1996,42(1):236-244
34. Marcuccilli, C.J. and Miller, R.J., CNS stress response: too hot to handle? Trends Neurosci, 17 (1994) : 135-138
35. Matta BF, Lam AM. The rate of blood withdrawal affects the accuracy of jugular venous bulb. Oxygen saturation measurements. Anesthesiology, 1997,86(4):806-808
36. Mcewen BS. Stress and aging hippocampus. Front Neuroendocrinol, 1999, 20:49-70
37. Meixenberger J, Meister T, Janka M, et al. Factors influencing morbidity and after cranial meningioma surgery - a multivariate analysis. Acta Neruochir, 1996,65(Suppl):99-101
38. Min L, Juntain Z. Effects of ginsenosides Rb_1 and Rg_1 on synaptosomal free calcium level, ARPase, and calmodulin in rat
hippocampuss. Chin Med (Engl), 1995,108:544-547
39. Mitasmi A, Audou Y, Matsuda S, et al. Original of ischemiainduced glutamate flux in the CA_1 field of the gerbil hippocampuss: an in vitro brain dialysis study. Neuro Chem, 1994,63:2152
40. Nadeau K, Das A, Walsh CT. Hsp90 chaperonins possess ATPase activity and bind heat shock transcription factors and peptidyl prolyl isomerases, J Biol Chem, 1993,268:1479-1487
41. Nagafuji T, Matsui J, Koide T, et al. Blockade of nitric oxide formation by Nomega-nitro-Ⅰ-arginine mitigates ischemic brain edema and subsequent cerebral infarction in rats. Neurosci Lett, 1992,147:159
42. Nathan C. Nitric oxide as secretory product of mammalian cells. FASEB, 1992,6:3051
43. Oberley LW, Buettner R. Role of superoxide dismutase in cancer: a rivew. Cancer Res, 1979,39:1141
44. Park TS, Gonzaks ER, Gidday JM. Platelet-activating factor mediates ischemia-induced leukocgte endothelial adherence in new born pig brain. J Cereb Blood Flow Metab, 1999,19 (4):417-442
45. Picard D, Khursheed B, Garabedian MJ, et al. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature, 1990;348:166-168
46. Rose DW, Welch WJ, Kramer G. et al. Possible involvement of the 90-kDa heat shock protein in the regulation of protein synthesis. J Biol Chem, 1989,264:6239-6244
47. Rutherford SL, Zuker CS. Protein folding and the regulation of signaling pathways. Cell, 1994;79 : 1129-1132
48. Schell RM, Kern FH, Reves JR.The role of continuous jugular venous saturation monitoring during cardic surgery with cardiopulomary bypass. Anesth Analg, 1992;74:627-629
49. Sharp FR, Sagar SM. Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene respone. Neutoxicology, 1994,15(1):51-59
50. Sheng H, Brady TC, Pearlstein RD, et al. Extracellular superoxide disutase deficiency worsens outcome from focal cerebral ischemia in the mouse. Neurosci Lett, 1999;267 (1):13-16
51. Siddique MS, Eddeb F, Mantle D, et al. Extracts of Ginkgo biloba and Panax ginseng protect brain proteins from free radical induced oxidative damage in vitro. Acta Neurochir Suppl, 2000;76:87-90
52. Sutton LN, Mclaughin AC, Dante S, et al. Cerebral venous oxygen content as a measure of srain energy metabolism with increased intraeranial pressure and hyperventilation. J Neurosurg, 1990;73:927-932
53. Wen TC, Yoshimura, Matsuda S, et al. Ginseng root prevents learning disability and neuronal loss in gerbils with 5-min at forebrain ischemia. Acta Neuropathol, 1996;91: 15-22
54．陈斌，吴国祥，汪保华等．亚低温对大鼠脑缺血再灌注损伤后HSP70 mRNA表达及损伤神经细胞凋亡的影响．卒中与神经疾病杂志，2001；8(6)：332-333
55．陈东，赵贵德，考宏盛．缺血性脑卒中发病机制研究新进展．国外医学神经病学神经外科学分册，2001；28(1)：32-34
56．陈嘉峰，宗瑞义，陈声武．人参皂甙对急性脑缺血脑内能量代谢的影响．白求恩医科大学学报，1992；18(6)：538-539
57．陈嘉峰，刘岷，陈声武．急性脑缺血组织Ach，ChAT的变化及人参皂甙的影响．中风与神经疾病杂志，1998；15(3)：157-158
58．陈晴晖，陈穗，陈韩秋等．中药防治脑缺血／再灌注损伤的研究进展．实用医学杂志，1998；14(11)：850-851
59．陈绍洋，熊利泽，曾祥龙．麻醉和手术中脑氧供需平衡研究进展．解放军医学杂志，2002；2：187-188
60．储国平．人参皂甙抗脂质过氧化作用及对大鼠脑灌注损伤的保护作用．中国药理学报，1990；11(2)：119-121
61．褚文政，曹秋云．大鼠局灶性脑缺血再灌注损伤后HSP70的表达及与细胞凋亡的关系．滨州医学院学报，2000；23(6)：525-527
62．戴晓明，吴晓群，刘学风等．参附、柴胡注射液对肾缺血再灌注损伤的影响．江苏中医，1998；19(2)：46-47
63．郭建巍，蔡美英．HSP70抗原呈递分子的研究进展．微生物免疫学进展，2000；28(3)：95-98
64．郭怡莲，刘仁光．参附注射液对兔心肌缺血再灌注损伤内皮功能的影响．中国中医急症，2003；2(1)：18-19
65．韩曙君，熊利泽，曾祥龙．分子血红蛋白的脑保护作用研究．国外医学麻醉与复苏分册，1997；18(6)：354-356
66．贾红慧，吴向东．参附注射液研究进展．中成药，1993：2：35-36
67．江光明．参附、参脉注射液研究述评．湖南中医药学导报，1995；1(2)：36-38
68．黄艳军，晋光荣．脑缺血中细胞凋亡的多元调节及其保护机制．国外医学脑血管疾病分册，2002；10(1)：69-71
69．姜正林，陈益仁，周纯等．人参皂甙抗缺氧缺血性脑损伤的谷氨酸相关机制．中国应用生理学杂志，2001；17(2)：105-109
70．林兆奋，缪明永，王学敏．一氧化氮合酶抑制剂对鼠脑缺血再灌注后线粒体呼吸功能的保护作用．神经解剖学杂志，
1998；14(3)：119
71．李建生，马玉羡，郭剑锋．中药防治脑缺血再灌注损伤的研究进展．河南中医药学刊，1999；14(2)：61-65
72．李冬梅，许逸，傅石玉等．人参皂甙Rg_1对脑缺血大鼠软脑膜微循环的影响．微循环杂志，1999；9(1)：8-11
73．李源，陈震需，谢安等．川芎嗪对脑缺血再灌注损伤热休克蛋白70表达的影响．中华内科杂志，1998；37(5)：333-335
74．李文放，陈洁，吴静．参附注射液对感染性休克的氧输送及右心室功能变化的作用．中国急救医学杂志，2001；21(8)：477-478
75．廖维靖，Frank W．脑缺血损伤的病理生理机制-损伤级联反应．国外医学脑血管疾病分册，1998；6(4)：197-202
76．刘贵明，王多友，张秉钧．颈内静脉血氧饱和度监测的临床应用．国外医学麻醉与复苏分册，1999；20(3)：164-167
77．刘红朝，董芳永，雷霆．脑肿瘤患者生存质量的评估．中国临床康复，2001；6(10)：1396-1397
78．刘鸣．卒中防治的研究证据——预防进展更加令人鼓舞．国外医学脑血管疾病分册，2001；9(4)：195
79．刘青云，宋军，陈绍冀．中药治疗缺血性中风的研究进展．中国中西医结合杂志，2000；20(4)：309-312
80．刘先义，邹捍东，余金甫等．参附注射液对缺血再灌注家兔多脏器损伤的治疗作用．中华麻醉学杂志，1997；17(7)：430-432
81．路志红，熊利泽，王强等．刺五加注射液对大鼠大脑中动脉栓塞所致脑缺血损伤的保护作用研究．第四军医大学学报，2002；22(8)：378-380
82．罗巍，万兰青，马超英等．参附注射液对兔内毒素休克肺损伤的保护作用．中国危重病急救医学，1995；7(2)：68-70
83．麻兴利，徐启明，刘钟淑．中药提取成分对脑缺血／再灌注损伤防治作用．中国中西医综合杂志，1993：13(11)：699-701
84．欧阳文，徐启明，蔡宏伟．脑缺血再灌注损伤与热休克蛋白70(HSP70)基因的表达．国外医学麻醉与复苏分册，1998；20(5)：307-310
85．潘树义，王苏平，钟世镇．神经细胞损害机制和保护治疗的若干进展．国外医学脑血管疾病分册，2001；9(1)：24-27
86．潘鑫鑫，张明霞．人参皂甙对急性脑缺血的保护作用．南京医学学报，1992；12(3)：237-239
87．申奥，刘茂鼎，汪涛等．999参附注射液对血液流变学影响的临床观察．辽宁中医杂志，2001；28(5)：295
88．石记才，夏晓红，薛玉凤等．参附注射液对热缺血肾保护作用的实验研究．中华泌尿外科杂志，1990；11(5)：291-293
89．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织兴奋性氨基酸递质和钙代谢的影响．脑与神经疾病杂志，1999；7(1)：5-7
90．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织Na~+-K~+-ATPase活性的影响．第四军医大学学报，1999；20(8)：676-677
91．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织氧自由基和SOD的影响．临床神经疾病杂志，1999；12(4)：199-201
92．唐晓平，张跃康，余定庸等．参附注射液对治疗急性重型脑外伤的临床观察．川北医学院学报，2003；18(2)：78-81
93．陶兰薇，鲁斌，郑灏泳等．热休克蛋白HSP70在MCAO大鼠脑中的表达．天津医科大学学报，2001；7(3)：366-368
94．田有勇，方思羽，张苏明．单胺类递质与脑缺血．卒中与神经疾病杂志，1999；6(Suppl)：23-25
95．王军，熊利泽，宋立强等．全身亚低温对大鼠全脑缺血／再灌注海马CAl区凋亡的影响．第四军医大学学报，
1999；20(6)：534-536
96．王强，陈绍洋，熊利泽．川芎嗪防止缺血性脑损伤的机制研究．陕西医学，2001；30(4)：223-225
97．王正荣，杨芳炬，徐彬等．参附注射液对大鼠肠系膜微循环的作用．中华药理与临床，2001；17(4)：8-9
98．吴新民，姜正林，陈益仁等．人参皂甙抗缺氧缺血性脑损伤作用与抑制谷氨酸释放有关．南通医学院学报，2000；20(4)：346-347
99．夏中元，郑利民．参附注射液防护肠粘膜缺血再灌注损伤的实验研究．中华创伤杂志，2001；17(4)：235-236
100．熊利泽，路志红．重复电针预处理可减轻大鼠急性短暂性脑缺血损伤．第四军医大学学报，2001，22(21)：封2
101．熊利泽，朱正华，董海龙等．异氟醚预处理对大鼠局灶性脑缺血损伤的保护作用．中华麻醉学杂志，2000，20(12)：730-733
102．熊利泽，Nakakimura K，曾祥龙．双阿司匹林交联血红蛋白的脑保护作用研究及评价．国外医学脑血管疾病分册，1998；6(6)：326～329
103．许川山，吴士明．热休克蛋白表达与脑缺血性损害．现代康复，2000；4：1694-1695
104．薛燕，白金叶，程桂芳．参附注射液对免疫功能的影响．中药药理与临床，2001；17(1)：8-9
105．杨树龙，冯志强，邬丽莎等．参附注射液对家兔急性肾缺血再灌注损伤的预防作用及机理研究．中国病理生理杂志，2003；19(3)：353-356
106．余永华，戈燕，杨树华等．参附注射液对肢体缺血／再灌注脂质过氧化反应的影响．中华医学全科杂志，2003；2(1)：18-19
107．张春芬，李建美，伦学庆等．血清锰超氧化物歧化酶与颅脑肿瘤关系的研究．中国肿瘤临床与康复，1996；3(2)：13-14
108．张均田，段文贞，吴俊芳．细胞凋亡的基因调控和抗神经细胞凋亡剂的研究．药学学报，1998；33(1)：75-79
109．张民，刘剑波，张洪亮等．电针预处理及联合参附注射液对局灶性脑缺血大鼠的保护作用．上海针灸杂志，2003；22(7)：10-13
110．章培军，吕永利，赖红等．氧自由基损伤海马神经元及人参皂甙的保护作用．解剖科学进展，2000；3：264-266
111．张英鸽．人参总皂甙对大鼠脑缺血再灌注损伤的保护作用．中国药理学与毒理学杂志，1994；8(1)：12-18
112．张运周，尹岭，朱克．缺血半暗带的神经影像学判定．国外医学脑血管疾病分册，2001；9f5)：274-276
113．赵克然，杨毅军，曹道峻．氧自由基与临床．北京，中国医药科技出版社，1999：297
114．郑传东，闵苏．参附注射液对全麻病人催醒作用的临床研究．临床麻醉学杂志，2003；19(11)：683-684
115．郑玉，熊利泽，吴明春等．异氟醚预处理联合参附注射液对大鼠短暂性局灶性脑缺血损伤协同保护作用的研究．中国中西医结合急救杂志，2001；8(6)：338-340
116．郑玉，熊利泽，朱正华等．参附注射液对大鼠短暂性局灶性脑缺血损伤的治疗时间窗研究．第四军医大学学报，2002；23(15)：1353-1356
117．朱海波，方文龙．人参皂甙单体Re对急性脑缺血—再灌注损伤的保护作用．延边医学院学报，1993；16(1)：20-21
118．朱正华，熊利泽，董海龙等．参附注射液对兔脊髓缺血性损伤的保护作用．第四军医大学学报，2000；21(3)：278-282
119．朱正华，熊利泽，董海龙等．参附注射液对兔脊髓缺血性损伤保护作用的量效关系研究．中华麻醉学杂志，2000；21(11)：664-668
120．朱正华，熊利泽，董海龙等．参附注射液对大鼠短暂性局灶性脑缺血损伤的保护作用．中国中西医结合急救杂志，2001；8：79-81
2. Andrews PJD, Dearden NM, Miller JD. Jugular bulb cannulation technique validation of a new continuous monitor. Br J Anaesth, 1991;67:533-558
3. Andrews RJ, Bringas JR A. review of srain retpaction and recommendations for minimizing intraoperative brain injury. Neurosurgery, 1993;33: 1052
4. Aoke M, Age K, Kavague J, et al. The preconditioned hippocampus accelerates HSP70 heat shock gene expression following transient ischemia in gerbils. Neurosci Lett, 1993,155(1):7-10
5. Aronowski J, Grotta JC, Waxham MN, et al. Ischemia-induced translocation of Ca~(2+)/calmodulin-dependent protein kinase Ⅱ: potential role in neuronal damage. Neurochem, 1992,58(5): 1743
6. Attle AS, Wu JA, Yuan CS. Ginseng pharmacology: Multiple constituents and multiple actions. Biochem Pharmacol, 1999,58:1685-1693
7. Barber DA, Hamis SR. Oxygen free radical and antioxidants: A review. Am Pham, 1994,34(9):26-35
8. Baron JC. Mapping the ischemic penumbra with PET:implications for acute stroke treatment. Cerebrovasc Dis, 1999, 9(4):193-201
9. Chan PH. Role of oxidants in ischemia brain damage. Stroke, 1996; 27:1124-1129.
10. Chen J, Graham SH, Zhu RL, et al. Stress proteins and tolerance
to focal cerebral ischemia. J Cereb Blood Flow Metab 1996,16(3):566-577.
11. Chen SY, Wang Q, Zeng XL, et al. The effect of PaCO_2 on the balance of cerebral oxygen supply and consumption during intravenous gerneral anesthesia. J Med Coll PLA,1999;14(4):274-277.
12. Collard CD, Vakeva A, Morrissey MA, et al. Complement activation after oxidative stresss: role of the lectin complement pathway. Am J Pathol, 2000,156(5): 1549-1556.
13. Coyle JT, Puttfarcken P. Oxidative stresss, glutamate, and the neurodegenerative discorders. Science, 1993,262:689
14. Cruz J, Jaggi JT, Hoffstad OJ. Cerebral blood flow and oxygen consumption in acute brain injury with acute anemia: an alternative for the cerebral metabolic rate of oxygen consumption? Crit Care Med,1993,21:1218-1214
15. De Jesus O, Sekhar LN, Parikh HK, et al. Long-term follow up of patients with meningiomas involving the cavernous sinus: Recurrence, progression, and quality of life. Neurosurgery, 1996,39:915-920.
16. Facob RA, Burri BJ. Oxidative damage and defence. Am J Clin Nutr, 1996,63(6):9805-9853.
17. Fisher M, Schaebitz W. An overview of acute stroke therapy: past, present, and future. Arch Intern Med 2000; 160(21): 3196-3206.
18. Fourie AM, Hupp YR, Lane DP. HSP70 binding sites in the tumor suppressor protein P53. J Biol Chem,1997;272(40): 19471-19479.
19. Gastagne V, Gautschi M, Lefevre K, et al. Relationshiop between neuronal death and cellullar redos status. Focus on the
developing nervous system. Prog Neurobiol, 1999, 59:397-423.
20. Higashi T, Takechi H., Uemura Y, et al. Differential induction of mRNA species encoding several classes of stress proteins following focal cerebral ischemia in rats, Brain Res, 1994,650:239-248
21. Huang KC. The pharmacology of Chinese herbs. CRC Press, Boca Raton, FL, 1999
22. Hutchison, KA, Dittmar, KD Pratt, WB. All of the factors required for assembly of the glucocorticoid receptor into a functional heterocomplex with heat shock protein 90 are preassociated in a self-sufficient protein folding structure, a foldosome, J Biol Chem., 1994,269:27894-27899
23. Jarskog LF, Gilmore JH. Developmental expression of Bel-2 protein in human cotex. Brain Res Dev Brain Res, 2000,119: 225-230
24. Jiang XY, Zhang JT, Shi CZ. Mechanism of action of ginsenoside Rb_1 in decreasing intracellular Ca~(2+). Acta Pharm Sin, 1996,31:321-326
25. Jonathan W, Graham M. Management of severe head injury, Contemporary Neurosurgery, 1996,18:1～5
26. Kader A, Frazzini VI, Solomon RA, et al. Nitric Oxide production during cerebral ischemia in rats. Stroke, 1993,24:1709
27. Kato H, Kanellopoulos GK, Matsuo S, et al. Neuronal apoptosiss and necrosis following spinal cord ischemia in the rat. Exp Neurol, 1998, 148(2):464-474
28. Kawagoe J, Abe K., Aoki M et al. Induction of HSP90 (?)heat shock mRNA after transient global ischemia in gerbil hippocampus, Brain Res, 1993, 621:121-125
29. Kim CS, Park JB, Kim KJ, et al. Effect of Korea red ginseng on cerebral blood flow and superoxide production. Acta Pharmacol Sin, 2002;23(12): 1152-1156
30. Kinouch H, Sharp FR, Hill MP, et al. Induction of 70-kDa heat shock protein and HSP70 mRNA following transient focal cerebral ischemia in the rat. Cereb Blood Metab, 1993; 13(1): 105-115
31. Kinuta Y, Kinmura M, Tokawa Y, et al. Change in xanthine oxidase in ischemic rat brain. J Neurosurg, 1989,71 (3):417
32. Lim JH, Wen TC, Metsuda s, et al. Protection of ischemic hippocampal neurons by ginsenoside Rb_1, a main ingredient of ginseng root. Neurosci Res 1997; 28:191-200
33. Marcus JD, Yolanda CM, Benjamin SA, et al. Focal cerebral ischemia increase the levels of several classes of heat shock proteins and their corresponding mRNAs. Molecular Brain Research, 1996,42(1):236-244
34. Marcuccilli, C.J. and Miller, R.J., CNS stress response: too hot to handle? Trends Neurosci, 17 (1994) : 135-138
35. Matta BF, Lam AM. The rate of blood withdrawal affects the accuracy of jugular venous bulb. Oxygen saturation measurements. Anesthesiology, 1997,86(4):806-808
36. Mcewen BS. Stress and aging hippocampus. Front Neuroendocrinol, 1999, 20:49-70
37. Meixenberger J, Meister T, Janka M, et al. Factors influencing morbidity and after cranial meningioma surgery - a multivariate analysis. Acta Neruochir, 1996,65(Suppl):99-101
38. Min L, Juntain Z. Effects of ginsenosides Rb_1 and Rg_1 on synaptosomal free calcium level, ARPase, and calmodulin in rat
hippocampuss. Chin Med (Engl), 1995,108:544-547
39. Mitasmi A, Audou Y, Matsuda S, et al. Original of ischemiainduced glutamate flux in the CA_1 field of the gerbil hippocampuss: an in vitro brain dialysis study. Neuro Chem, 1994,63:2152
40. Nadeau K, Das A, Walsh CT. Hsp90 chaperonins possess ATPase activity and bind heat shock transcription factors and peptidyl prolyl isomerases, J Biol Chem, 1993,268:1479-1487
41. Nagafuji T, Matsui J, Koide T, et al. Blockade of nitric oxide formation by Nomega-nitro-Ⅰ-arginine mitigates ischemic brain edema and subsequent cerebral infarction in rats. Neurosci Lett, 1992,147:159
42. Nathan C. Nitric oxide as secretory product of mammalian cells. FASEB, 1992,6:3051
43. Oberley LW, Buettner R. Role of superoxide dismutase in cancer: a rivew. Cancer Res, 1979,39:1141
44. Park TS, Gonzaks ER, Gidday JM. Platelet-activating factor mediates ischemia-induced leukocgte endothelial adherence in new born pig brain. J Cereb Blood Flow Metab, 1999,19 (4):417-442
45. Picard D, Khursheed B, Garabedian MJ, et al. Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature, 1990;348:166-168
46. Rose DW, Welch WJ, Kramer G. et al. Possible involvement of the 90-kDa heat shock protein in the regulation of protein synthesis. J Biol Chem, 1989,264:6239-6244
47. Rutherford SL, Zuker CS. Protein folding and the regulation of signaling pathways. Cell, 1994;79 : 1129-1132
48. Schell RM, Kern FH, Reves JR.The role of continuous jugular venous saturation monitoring during cardic surgery with cardiopulomary bypass. Anesth Analg, 1992;74:627-629
49. Sharp FR, Sagar SM. Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene respone. Neutoxicology, 1994,15(1):51-59
50. Sheng H, Brady TC, Pearlstein RD, et al. Extracellular superoxide disutase deficiency worsens outcome from focal cerebral ischemia in the mouse. Neurosci Lett, 1999;267 (1):13-16
51. Siddique MS, Eddeb F, Mantle D, et al. Extracts of Ginkgo biloba and Panax ginseng protect brain proteins from free radical induced oxidative damage in vitro. Acta Neurochir Suppl, 2000;76:87-90
52. Sutton LN, Mclaughin AC, Dante S, et al. Cerebral venous oxygen content as a measure of srain energy metabolism with increased intraeranial pressure and hyperventilation. J Neurosurg, 1990;73:927-932
53. Wen TC, Yoshimura, Matsuda S, et al. Ginseng root prevents learning disability and neuronal loss in gerbils with 5-min at forebrain ischemia. Acta Neuropathol, 1996;91: 15-22
54．陈斌，吴国祥，汪保华等．亚低温对大鼠脑缺血再灌注损伤后HSP70 mRNA表达及损伤神经细胞凋亡的影响．卒中与神经疾病杂志，2001；8(6)：332-333
55．陈东，赵贵德，考宏盛．缺血性脑卒中发病机制研究新进展．国外医学神经病学神经外科学分册，2001；28(1)：32-34
56．陈嘉峰，宗瑞义，陈声武．人参皂甙对急性脑缺血脑内能量代谢的影响．白求恩医科大学学报，1992；18(6)：538-539
57．陈嘉峰，刘岷，陈声武．急性脑缺血组织Ach，ChAT的变化及人参皂甙的影响．中风与神经疾病杂志，1998；15(3)：157-158
58．陈晴晖，陈穗，陈韩秋等．中药防治脑缺血／再灌注损伤的研究进展．实用医学杂志，1998；14(11)：850-851
59．陈绍洋，熊利泽，曾祥龙．麻醉和手术中脑氧供需平衡研究进展．解放军医学杂志，2002；2：187-188
60．储国平．人参皂甙抗脂质过氧化作用及对大鼠脑灌注损伤的保护作用．中国药理学报，1990；11(2)：119-121
61．褚文政，曹秋云．大鼠局灶性脑缺血再灌注损伤后HSP70的表达及与细胞凋亡的关系．滨州医学院学报，2000；23(6)：525-527
62．戴晓明，吴晓群，刘学风等．参附、柴胡注射液对肾缺血再灌注损伤的影响．江苏中医，1998；19(2)：46-47
63．郭建巍，蔡美英．HSP70抗原呈递分子的研究进展．微生物免疫学进展，2000；28(3)：95-98
64．郭怡莲，刘仁光．参附注射液对兔心肌缺血再灌注损伤内皮功能的影响．中国中医急症，2003；2(1)：18-19
65．韩曙君，熊利泽，曾祥龙．分子血红蛋白的脑保护作用研究．国外医学麻醉与复苏分册，1997；18(6)：354-356
66．贾红慧，吴向东．参附注射液研究进展．中成药，1993：2：35-36
67．江光明．参附、参脉注射液研究述评．湖南中医药学导报，1995；1(2)：36-38
68．黄艳军，晋光荣．脑缺血中细胞凋亡的多元调节及其保护机制．国外医学脑血管疾病分册，2002；10(1)：69-71
69．姜正林，陈益仁，周纯等．人参皂甙抗缺氧缺血性脑损伤的谷氨酸相关机制．中国应用生理学杂志，2001；17(2)：105-109
70．林兆奋，缪明永，王学敏．一氧化氮合酶抑制剂对鼠脑缺血再灌注后线粒体呼吸功能的保护作用．神经解剖学杂志，
1998；14(3)：119
71．李建生，马玉羡，郭剑锋．中药防治脑缺血再灌注损伤的研究进展．河南中医药学刊，1999；14(2)：61-65
72．李冬梅，许逸，傅石玉等．人参皂甙Rg_1对脑缺血大鼠软脑膜微循环的影响．微循环杂志，1999；9(1)：8-11
73．李源，陈震需，谢安等．川芎嗪对脑缺血再灌注损伤热休克蛋白70表达的影响．中华内科杂志，1998；37(5)：333-335
74．李文放，陈洁，吴静．参附注射液对感染性休克的氧输送及右心室功能变化的作用．中国急救医学杂志，2001；21(8)：477-478
75．廖维靖，Frank W．脑缺血损伤的病理生理机制-损伤级联反应．国外医学脑血管疾病分册，1998；6(4)：197-202
76．刘贵明，王多友，张秉钧．颈内静脉血氧饱和度监测的临床应用．国外医学麻醉与复苏分册，1999；20(3)：164-167
77．刘红朝，董芳永，雷霆．脑肿瘤患者生存质量的评估．中国临床康复，2001；6(10)：1396-1397
78．刘鸣．卒中防治的研究证据——预防进展更加令人鼓舞．国外医学脑血管疾病分册，2001；9(4)：195
79．刘青云，宋军，陈绍冀．中药治疗缺血性中风的研究进展．中国中西医结合杂志，2000；20(4)：309-312
80．刘先义，邹捍东，余金甫等．参附注射液对缺血再灌注家兔多脏器损伤的治疗作用．中华麻醉学杂志，1997；17(7)：430-432
81．路志红，熊利泽，王强等．刺五加注射液对大鼠大脑中动脉栓塞所致脑缺血损伤的保护作用研究．第四军医大学学报，2002；22(8)：378-380
82．罗巍，万兰青，马超英等．参附注射液对兔内毒素休克肺损伤的保护作用．中国危重病急救医学，1995；7(2)：68-70
83．麻兴利，徐启明，刘钟淑．中药提取成分对脑缺血／再灌注损伤防治作用．中国中西医综合杂志，1993：13(11)：699-701
84．欧阳文，徐启明，蔡宏伟．脑缺血再灌注损伤与热休克蛋白70(HSP70)基因的表达．国外医学麻醉与复苏分册，1998；20(5)：307-310
85．潘树义，王苏平，钟世镇．神经细胞损害机制和保护治疗的若干进展．国外医学脑血管疾病分册，2001；9(1)：24-27
86．潘鑫鑫，张明霞．人参皂甙对急性脑缺血的保护作用．南京医学学报，1992；12(3)：237-239
87．申奥，刘茂鼎，汪涛等．999参附注射液对血液流变学影响的临床观察．辽宁中医杂志，2001；28(5)：295
88．石记才，夏晓红，薛玉凤等．参附注射液对热缺血肾保护作用的实验研究．中华泌尿外科杂志，1990；11(5)：291-293
89．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织兴奋性氨基酸递质和钙代谢的影响．脑与神经疾病杂志，1999；7(1)：5-7
90．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织Na~+-K~+-ATPase活性的影响．第四军医大学学报，1999；20(8)：676-677
91．宋立强，熊利泽，王军等．聚合牛血红蛋白对缺血／再灌注脑组织氧自由基和SOD的影响．临床神经疾病杂志，1999；12(4)：199-201
92．唐晓平，张跃康，余定庸等．参附注射液对治疗急性重型脑外伤的临床观察．川北医学院学报，2003；18(2)：78-81
93．陶兰薇，鲁斌，郑灏泳等．热休克蛋白HSP70在MCAO大鼠脑中的表达．天津医科大学学报，2001；7(3)：366-368
94．田有勇，方思羽，张苏明．单胺类递质与脑缺血．卒中与神经疾病杂志，1999；6(Suppl)：23-25
95．王军，熊利泽，宋立强等．全身亚低温对大鼠全脑缺血／再灌注海马CAl区凋亡的影响．第四军医大学学报，
1999；20(6)：534-536
96．王强，陈绍洋，熊利泽．川芎嗪防止缺血性脑损伤的机制研究．陕西医学，2001；30(4)：223-225
97．王正荣，杨芳炬，徐彬等．参附注射液对大鼠肠系膜微循环的作用．中华药理与临床，2001；17(4)：8-9
98．吴新民，姜正林，陈益仁等．人参皂甙抗缺氧缺血性脑损伤作用与抑制谷氨酸释放有关．南通医学院学报，2000；20(4)：346-347
99．夏中元，郑利民．参附注射液防护肠粘膜缺血再灌注损伤的实验研究．中华创伤杂志，2001；17(4)：235-236
100．熊利泽，路志红．重复电针预处理可减轻大鼠急性短暂性脑缺血损伤．第四军医大学学报，2001，22(21)：封2
101．熊利泽，朱正华，董海龙等．异氟醚预处理对大鼠局灶性脑缺血损伤的保护作用．中华麻醉学杂志，2000，20(12)：730-733
102．熊利泽，Nakakimura K，曾祥龙．双阿司匹林交联血红蛋白的脑保护作用研究及评价．国外医学脑血管疾病分册，1998；6(6)：326～329
103．许川山，吴士明．热休克蛋白表达与脑缺血性损害．现代康复，2000；4：1694-1695
104．薛燕，白金叶，程桂芳．参附注射液对免疫功能的影响．中药药理与临床，2001；17(1)：8-9
105．杨树龙，冯志强，邬丽莎等．参附注射液对家兔急性肾缺血再灌注损伤的预防作用及机理研究．中国病理生理杂志，2003；19(3)：353-356
106．余永华，戈燕，杨树华等．参附注射液对肢体缺血／再灌注脂质过氧化反应的影响．中华医学全科杂志，2003；2(1)：18-19
107．张春芬，李建美，伦学庆等．血清锰超氧化物歧化酶与颅脑肿瘤关系的研究．中国肿瘤临床与康复，1996；3(2)：13-14
108．张均田，段文贞，吴俊芳．细胞凋亡的基因调控和抗神经细胞凋亡剂的研究．药学学报，1998；33(1)：75-79
109．张民，刘剑波，张洪亮等．电针预处理及联合参附注射液对局灶性脑缺血大鼠的保护作用．上海针灸杂志，2003；22(7)：10-13
110．章培军，吕永利，赖红等．氧自由基损伤海马神经元及人参皂甙的保护作用．解剖科学进展，2000；3：264-266
111．张英鸽．人参总皂甙对大鼠脑缺血再灌注损伤的保护作用．中国药理学与毒理学杂志，1994；8(1)：12-18
112．张运周，尹岭，朱克．缺血半暗带的神经影像学判定．国外医学脑血管疾病分册，2001；9f5)：274-276
113．赵克然，杨毅军，曹道峻．氧自由基与临床．北京，中国医药科技出版社，1999：297
114．郑传东，闵苏．参附注射液对全麻病人催醒作用的临床研究．临床麻醉学杂志，2003；19(11)：683-684
115．郑玉，熊利泽，吴明春等．异氟醚预处理联合参附注射液对大鼠短暂性局灶性脑缺血损伤协同保护作用的研究．中国中西医结合急救杂志，2001；8(6)：338-340
116．郑玉，熊利泽，朱正华等．参附注射液对大鼠短暂性局灶性脑缺血损伤的治疗时间窗研究．第四军医大学学报，2002；23(15)：1353-1356
117．朱海波，方文龙．人参皂甙单体Re对急性脑缺血—再灌注损伤的保护作用．延边医学院学报，1993；16(1)：20-21
118．朱正华，熊利泽，董海龙等．参附注射液对兔脊髓缺血性损伤的保护作用．第四军医大学学报，2000；21(3)：278-282
119．朱正华，熊利泽，董海龙等．参附注射液对兔脊髓缺血性损伤保护作用的量效关系研究．中华麻醉学杂志，2000；21(11)：664-668
120．朱正华，熊利泽，董海龙等．参附注射液对大鼠短暂性局灶性脑缺血损伤的保护作用．中国中西医结合急救杂志，2001；8：79-81