人参皂甙Rb_1治疗大鼠脊髓缺血再灌注损伤的实验研究
摘要
脊髓损伤(spinal cord injury, SCI)是由直接或间接外力损伤脊髓，在损害相应的阶段出现各种功能障碍为主要临床表现一种称谓。它是一种高致残性疾病，脊髓损伤是一种严重的神经系统创伤，是常见的截瘫原因之一。脊髓缺血再灌注损伤（spinal cord ischemic reperfusioninjury，SCII）是原发性脊髓损伤的继发性损害，由Allen在1911年首先描述。它是指在一些导致脊髓缺血因素去除后，脊髓恢复血供，神经功能不仅得不到改善，反而在原缺血损伤基础上进一步加重，甚至出现不可逆性脊髓神经元迟发性死亡的现象，是外科手术常见并发症之一，特别是主动脉瘤、骶管肿瘤手术后，常需阻断主动脉，从而导致脊髓损伤，术后出现神经功能损伤的发病率高于4%，甚至可高达38%。脊髓缺血再灌注损伤是一个极其复杂的病理过程，确切的分子和细胞机制尚不清楚，目前认为与组织兴奋性氨基酸的释放、自由基的产生、胞内Ca2+的超载、Na+-K+-ATP平衡紊乱、炎症反应、神经细胞的凋亡等因素有关。各种因素共同存在、交互作用，致使组织细胞受损。
人参，五加科人参属植物人参（Panax ginseng C.A. Mey.）的根，是一种极具药用和食用价值的名贵中草药，应用距今已有2000余年的历史。人参中含有多种成分如人参皂甙、挥发油、有机酸及脂(软脂酸、硬脂酸、油酸和亚油酸)、甾醇及其甙、蛋白质、多肽、氨基酸及腐胺、精胺等其他许多含氨化合物、维生素类（维生素A、B1、B2和C等）、微量元素类、木质素、黄铜类、糖类、糖蛋白以及其他许多成分。近年来国内外学者对人参化学、药理及临床应用进行了大量的研究，证实人参皂甙是人参生理活性最重要的有效成分，且因糖基的组成和与甙元的连接位置不同，致使不同的人参皂甙所具有的药理学活性存在较大差异。包括抗肿瘤、抗衰老、抗心律失常、抑制细胞凋亡、降糖降脂、改善学习记忆、增强性功能和免疫功能及解酒等多个方面。
本研究拟通过建立大鼠脊髓缺血再灌注损伤模型，应用TheBasso Beattie Bresnahan（BBB）评分系统对脊髓神经功能进行评价；HE染色，尼氏体染色，Tunel凋亡检测等方法明确神经细胞形态变化及凋亡情况；应用免疫荧光、western blot等手段检测凋亡相关蛋白Bcl-2、Bax、磷酸化ASK-1及Caspase-3的表达情况。同时给予人参皂甙Rb1进行干预，观察人参皂甙Rb1干预对上述观测指标的影响，明确凋亡相关蛋白Bcl-2、Bax、磷酸化ASK-1及Caspase-3、人参皂甙Rb1和SCII三者间的作用及其可能机制，为临床研发新型治疗SCII的药物提供理论基础。
目的：探讨人参皂甙Rb1通过抗细胞凋亡作用治疗大鼠脊髓缺血再灌注损伤的研究。
方法：选用成年SD大鼠，雌雄各半，分为空白组、假手术组、治疗组（10mg/kg剂量每日给予人参皂甙Rb1腹腔注射）、模型组。采用夹闭腹主动脉的方法制备SCII模型。分别于再灌注后1d、2d、3d、4d、5d、6d、7d对四组模型进行The Basso Beattie Bresnahan(BBB)运动功能评分。缺血再灌注损伤1、3、5、7天后，分别取大鼠脊髓进行HE染色、尼氏体染色、Tunel法、免疫荧光化学和Westernblot检测，观察各组脊髓组织形态和凋亡情况及凋亡相关蛋白的表达情况。
结果：HE染色和尼氏体染色表明治疗组病理组织形态改变明显好于模型组。Tunel结果表明治疗组细胞凋亡率显著低于模型组（P<0.05）。Bax/Bcl-2比值治疗组显著低于模型组（P<0.05），磷酸化ASK-1、Caspase-3蛋白表达治疗组显著低于模型组（P<0.05）。Westernblot检测结果显示空白组和假手术组两组的p-ASK-1和Caspase-3蛋白表达较少；模型组中p-ASK-1和Caspase-3的蛋白表达明显增多，与空白组及假手术组相比有显著性差异（P＜0.05）；治疗组p-ASK-1和Caspase-3蛋白表达随着时间推移逐渐减少，且各个时间点与模型组相比均有显著性差异（P＜0.05）。
结论：人参皂甙Rb1可以治疗大鼠脊髓缺血再灌注损伤；人参皂甙Rb1可以促进Bcl-2蛋白的表达，且可以抑制Bax、p-ASK-1和Caspase-3蛋白的表达；抗凋亡作用可能是人参皂甙Rb1治疗大鼠脊髓缺血再灌注损伤的作用机制之一。
Spinal cord injury (SCI) is caused by directly or indirectly force,which often result in some clinical manifestations such as neurologicaldysfunction in the injuryed segments. SCI is not only a highly disablingdisease, but a common causes of paraplegia. Spinal cord ischemicreperfusion injury (SCII) is the secondary injury after the spinal cordprimary injury, which was first reported by Allen in1911. SCII refers towhen the spinal cord blood supply was restored after the removal ofspinal ischemic causes, neurological dysfunction not only can not beimproved but further aggravated base on the ischemic injury, and evencause the irreversible spinal neurons delayed death. SCII is a commoncomplication of surgery operation, especially of some operations whichneed to blocking the aorta, such as operations associated with aneurysmaortic and sacral canal tumor. The post operation incidence rate of nerveinjury is more than4%, even up to38%. SCII is a extremely complexpathological process, the precise molecular and cellular mechanism areremain unclear. At present, studies suggest that SCII is related tofollowing factors, such as the release of excitatory amino acids and freeradical, intracellular Ca2+overload, Na pump disorders, inflammation,and neurons apoptosis. Those factors are existing together and areinteracting each other, finally result in the neurological damaged.
Ginseng, the root of the Araliaceae plant panax ginseng, is a rareherbal traditional medicine with medical and edible value, it has been utilized more than2000years.
Ginseng contains a variety of ingredients, such as ginseng saponin,volatile oils, organic acids and lipids (palmitic acid, stearic acid, oleicacid and linoleic acid), sterols and their glycosides, proteins, peptides,amino acids and putrescine, spermine ammonia, and many othercompounds, vitamins (vitamin A, B1, B2and C), trace elements, lignin,brass, sugars, glycoproteins. Recently, a lot of research have been appliedto study the chemistry characteristics, pharmacology mechanism andclinical application, which confirm that ginsenosides is the mostimportant active ingredient in ginseng. In addition, because of thedifferent components and connections of the aglycone glycosylationposition, there is a big difference between the pharmacologically activevarious ginsenosides. Such as anti-tumor, anti-aging, anti-arrhythmic,inhibition of apoptosis, reducing blood glucose and lipids, improvelearning and memory, enhance sexual function and immune function.
In this study, through the establishment of the rat spinal cordischemia-reperfusion injury model and the Basso Beattie Bresnahan(BBB) scoring system, we could evaluate the spinal cord neurologicalfunction. By using the HE staining, nissl body staining and the Tunelapoptosis detection, we could figure out the apoptosis status and themorphological modification of neuron. By using the Immunofluorescencetechnique and Western blot, we could detect some apoptosis associatedproteins, such as Bcl-2, Bax, P-ASK-1and Caspase-3. We useginsenosides Rb1to perform the intervention experiment, and detect themodification of those mentioned index after the Rb1application. Fromthose experiments, we can not only confirm the functions andrelationships among apoptosis associated proteins (Bcl-2, Bax,P-ASK-1and Caspase-3), ginsenosides Rb1and SCII, but also provide the theoretical basis for the development of novel SCII treatment medicine.
Objectives: To discuss the anti-apoptosis mechanism of the SCIItherapeutical effect of ginsenosides Rb1.
Methods:Taking adult SD rats, both male and female, divided intocontrol group, sham group, treatment group (10mg/kg per day,intraperitoneal injection of ginsenosides Rb1), SCII model group (Byoccluding the abdominal aorta). Assessing the Basso Beattie Bresnahan(BBB) motor function score in1,2,3,4,5,6,7days after the reperfusion offour groups respectively.1,3,5,7days after reperfusion, to observe the tissuemorphology, apoptosis status of spinal cord and apoptosis associated proteins,spinal cord from each groups were taken out and perform HE staining, Nisslstaining, Tunel dectection, immunofluorescence detection and Westren blot.
Results: HE and Nissl body staining results suggest that thepathological and morphological changes of treatment group is better thanSCII group. Tunel results suggest the apoptosis rate of treatment group islower than the SCII model group significantly (P<0.05). Bax/Bcl-2valueof treatment group is still lower than the SCII model group significantly(P<0.05). The P-ASK-1and Caspase-3expression level of treatmentgroup is lower than the SCII model group significantly (P<0.05). Westernblot results indicate that the P-ASK-1and Caspase-3expression level ofcontrol group and sham group is lower than the other two operationgroups. In SCII model group, the P-ASK-1and Caspase-3expressionlevel is higher than control group and sham group (P<0.05). In Rb1treatment group, the P-ASK-1and Caspase-3expression level aredecreased gradually as time goes by, compare with the SCII model group,the expression level in each time point are all different significantly(P<0.05).
Conclusion: Ginsenoside Rb1can treat spinal cord ischemia-reperfusion injury. Ginsenosides Rb1can promote the expression ofBcl-2, and inhibit the expression of Bax, p-ASK-1and Caspase-3. Theanti-apoptotic effects of ginsenosides Rb1is one of the probably treatmentmechanisms of SCII.
人参，五加科人参属植物人参（Panax ginseng C.A. Mey.）的根，是一种极具药用和食用价值的名贵中草药，应用距今已有2000余年的历史。人参中含有多种成分如人参皂甙、挥发油、有机酸及脂(软脂酸、硬脂酸、油酸和亚油酸)、甾醇及其甙、蛋白质、多肽、氨基酸及腐胺、精胺等其他许多含氨化合物、维生素类（维生素A、B1、B2和C等）、微量元素类、木质素、黄铜类、糖类、糖蛋白以及其他许多成分。近年来国内外学者对人参化学、药理及临床应用进行了大量的研究，证实人参皂甙是人参生理活性最重要的有效成分，且因糖基的组成和与甙元的连接位置不同，致使不同的人参皂甙所具有的药理学活性存在较大差异。包括抗肿瘤、抗衰老、抗心律失常、抑制细胞凋亡、降糖降脂、改善学习记忆、增强性功能和免疫功能及解酒等多个方面。
本研究拟通过建立大鼠脊髓缺血再灌注损伤模型，应用TheBasso Beattie Bresnahan（BBB）评分系统对脊髓神经功能进行评价；HE染色，尼氏体染色，Tunel凋亡检测等方法明确神经细胞形态变化及凋亡情况；应用免疫荧光、western blot等手段检测凋亡相关蛋白Bcl-2、Bax、磷酸化ASK-1及Caspase-3的表达情况。同时给予人参皂甙Rb1进行干预，观察人参皂甙Rb1干预对上述观测指标的影响，明确凋亡相关蛋白Bcl-2、Bax、磷酸化ASK-1及Caspase-3、人参皂甙Rb1和SCII三者间的作用及其可能机制，为临床研发新型治疗SCII的药物提供理论基础。
目的：探讨人参皂甙Rb1通过抗细胞凋亡作用治疗大鼠脊髓缺血再灌注损伤的研究。
方法：选用成年SD大鼠，雌雄各半，分为空白组、假手术组、治疗组（10mg/kg剂量每日给予人参皂甙Rb1腹腔注射）、模型组。采用夹闭腹主动脉的方法制备SCII模型。分别于再灌注后1d、2d、3d、4d、5d、6d、7d对四组模型进行The Basso Beattie Bresnahan(BBB)运动功能评分。缺血再灌注损伤1、3、5、7天后，分别取大鼠脊髓进行HE染色、尼氏体染色、Tunel法、免疫荧光化学和Westernblot检测，观察各组脊髓组织形态和凋亡情况及凋亡相关蛋白的表达情况。
结果：HE染色和尼氏体染色表明治疗组病理组织形态改变明显好于模型组。Tunel结果表明治疗组细胞凋亡率显著低于模型组（P<0.05）。Bax/Bcl-2比值治疗组显著低于模型组（P<0.05），磷酸化ASK-1、Caspase-3蛋白表达治疗组显著低于模型组（P<0.05）。Westernblot检测结果显示空白组和假手术组两组的p-ASK-1和Caspase-3蛋白表达较少；模型组中p-ASK-1和Caspase-3的蛋白表达明显增多，与空白组及假手术组相比有显著性差异（P＜0.05）；治疗组p-ASK-1和Caspase-3蛋白表达随着时间推移逐渐减少，且各个时间点与模型组相比均有显著性差异（P＜0.05）。
结论：人参皂甙Rb1可以治疗大鼠脊髓缺血再灌注损伤；人参皂甙Rb1可以促进Bcl-2蛋白的表达，且可以抑制Bax、p-ASK-1和Caspase-3蛋白的表达；抗凋亡作用可能是人参皂甙Rb1治疗大鼠脊髓缺血再灌注损伤的作用机制之一。
Spinal cord injury (SCI) is caused by directly or indirectly force,which often result in some clinical manifestations such as neurologicaldysfunction in the injuryed segments. SCI is not only a highly disablingdisease, but a common causes of paraplegia. Spinal cord ischemicreperfusion injury (SCII) is the secondary injury after the spinal cordprimary injury, which was first reported by Allen in1911. SCII refers towhen the spinal cord blood supply was restored after the removal ofspinal ischemic causes, neurological dysfunction not only can not beimproved but further aggravated base on the ischemic injury, and evencause the irreversible spinal neurons delayed death. SCII is a commoncomplication of surgery operation, especially of some operations whichneed to blocking the aorta, such as operations associated with aneurysmaortic and sacral canal tumor. The post operation incidence rate of nerveinjury is more than4%, even up to38%. SCII is a extremely complexpathological process, the precise molecular and cellular mechanism areremain unclear. At present, studies suggest that SCII is related tofollowing factors, such as the release of excitatory amino acids and freeradical, intracellular Ca2+overload, Na pump disorders, inflammation,and neurons apoptosis. Those factors are existing together and areinteracting each other, finally result in the neurological damaged.
Ginseng, the root of the Araliaceae plant panax ginseng, is a rareherbal traditional medicine with medical and edible value, it has been utilized more than2000years.
Ginseng contains a variety of ingredients, such as ginseng saponin,volatile oils, organic acids and lipids (palmitic acid, stearic acid, oleicacid and linoleic acid), sterols and their glycosides, proteins, peptides,amino acids and putrescine, spermine ammonia, and many othercompounds, vitamins (vitamin A, B1, B2and C), trace elements, lignin,brass, sugars, glycoproteins. Recently, a lot of research have been appliedto study the chemistry characteristics, pharmacology mechanism andclinical application, which confirm that ginsenosides is the mostimportant active ingredient in ginseng. In addition, because of thedifferent components and connections of the aglycone glycosylationposition, there is a big difference between the pharmacologically activevarious ginsenosides. Such as anti-tumor, anti-aging, anti-arrhythmic,inhibition of apoptosis, reducing blood glucose and lipids, improvelearning and memory, enhance sexual function and immune function.
In this study, through the establishment of the rat spinal cordischemia-reperfusion injury model and the Basso Beattie Bresnahan(BBB) scoring system, we could evaluate the spinal cord neurologicalfunction. By using the HE staining, nissl body staining and the Tunelapoptosis detection, we could figure out the apoptosis status and themorphological modification of neuron. By using the Immunofluorescencetechnique and Western blot, we could detect some apoptosis associatedproteins, such as Bcl-2, Bax, P-ASK-1and Caspase-3. We useginsenosides Rb1to perform the intervention experiment, and detect themodification of those mentioned index after the Rb1application. Fromthose experiments, we can not only confirm the functions andrelationships among apoptosis associated proteins (Bcl-2, Bax,P-ASK-1and Caspase-3), ginsenosides Rb1and SCII, but also provide the theoretical basis for the development of novel SCII treatment medicine.
Objectives: To discuss the anti-apoptosis mechanism of the SCIItherapeutical effect of ginsenosides Rb1.
Methods:Taking adult SD rats, both male and female, divided intocontrol group, sham group, treatment group (10mg/kg per day,intraperitoneal injection of ginsenosides Rb1), SCII model group (Byoccluding the abdominal aorta). Assessing the Basso Beattie Bresnahan(BBB) motor function score in1,2,3,4,5,6,7days after the reperfusion offour groups respectively.1,3,5,7days after reperfusion, to observe the tissuemorphology, apoptosis status of spinal cord and apoptosis associated proteins,spinal cord from each groups were taken out and perform HE staining, Nisslstaining, Tunel dectection, immunofluorescence detection and Westren blot.
Results: HE and Nissl body staining results suggest that thepathological and morphological changes of treatment group is better thanSCII group. Tunel results suggest the apoptosis rate of treatment group islower than the SCII model group significantly (P<0.05). Bax/Bcl-2valueof treatment group is still lower than the SCII model group significantly(P<0.05). The P-ASK-1and Caspase-3expression level of treatmentgroup is lower than the SCII model group significantly (P<0.05). Westernblot results indicate that the P-ASK-1and Caspase-3expression level ofcontrol group and sham group is lower than the other two operationgroups. In SCII model group, the P-ASK-1and Caspase-3expressionlevel is higher than control group and sham group (P<0.05). In Rb1treatment group, the P-ASK-1and Caspase-3expression level aredecreased gradually as time goes by, compare with the SCII model group,the expression level in each time point are all different significantly(P<0.05).
Conclusion: Ginsenoside Rb1can treat spinal cord ischemia-reperfusion injury. Ginsenosides Rb1can promote the expression ofBcl-2, and inhibit the expression of Bax, p-ASK-1and Caspase-3. Theanti-apoptotic effects of ginsenosides Rb1is one of the probably treatmentmechanisms of SCII.
引文
[1] Chevallier A. Encyclopedia of herbal medicine[M]. New York: DKPublishing,2000,1-53.
[2]张树臣主编,中国人参[M].上海:上海科技教育出版社,1992.
[3]丛登立，宋长春，徐景达.西洋参叶中20(S)-人参皂试-Rh4，Rh2和人参皂试-Rh3的分离与鉴定[J].中国药学杂志.2000,35(2):82-84.
[4]王本祥.人参的研究[M].天津：天津科学技术出版社，1988.3-4.
[5]窦德强，任杰，陈颖，等.商品人参根的化学成分研究[J].中国中药杂志,2003,28(6):522-524.
[6]姚新生，徐馁绪，陈英杰.人参成分的研究[J].中国药学年鉴,1991,23-25.
[7]姚新生.天然药物化学[M].北京：人民卫生出版社，1990.
[8]窦德强，靳玲，陈英杰.人参的化学成分及药理活性的研究进展与展望[J].沈阳药科大学学报,1999,16(2):151-156.
[9]杨云，冯卫生主编.中药化学成分提取分离手册[M].中国中医药出版社,1998:2.
[10] Dou DQ, Chen YJ, Liang LH, et al. Six New Dammarance-typeTriteprene Saponions from the levaes of Panxa ginseng.ChemPharmbull.2001,49(4):442-445.
[11]张春枝，安利佳，等.人参皂试生理活性的研究进展[J].食品与发酵工业,2003,28(4):70-74.
[12] Nicola Fuzzati. Analysis methods of ginsenosides[J]. Journal ofChromatography B,2004(812):119-133.
[13]朱丹妮，杨力，严永清.西洋参与人参中人参皂甙含量的比较.植物资源与环学报.2000,9(3):1-4.
[14]窦得强，靳玲，陈英杰.人参的化学成分及药理活性的研究进展与展望[J].沈阳药科大学学报,1999,16(2):151-156.
[15]王本详.人参研究进展[M].天津:天津科学技术出版社,1991.
[16]王铁生，常维春，尚培根，等.中国人参[M].辽宁：辽宁科学技术出版社,2001,677-679.
[17]杨玉琪，李玛琳.人参皂甙的抗肿瘤作用及其机制[J].药学进展,2003,27(5):287-290.
[18]张玲，单卫华，梁瑞雪，等.人参提取工艺研究[J].时珍国医国药,2000,11(9):777-779.
[19]吴正中，周国明，谢玉琼.正交试验法提取人参皂甙工艺的研究[J].中国药房,2003,27(5):287-290.
[20]张崇禧，郑友兰，张春红，等.大孔树脂吸附人参总皂成工艺及再生使用的研究[J].中国药学杂志,2003,38(9):661-664.
[21]]S.Youn Yuen, K. Ming Yu, C. Yuan Shim. Microwave-assistedextraction of ginsenosides from ginseng root[J].MicrochemicalJournal,2003,74(2):131-139.
[22]张镜澄.超临界流体萃取[M].北京:化学工业出版社,2000,102-123.
[23]高巨.树脂法提取三七叶皂甙及三七皂甙组分分离的研究[D].天津：南开大学高分子化学与物理,2005.
[24]朱萱萱，茅泳雯，何润霞，等.反相HPLC法测定药用人参中多种人参皂甙的含量[J].中国生化药物杂志,1998,19(1):28-31.
[25]王隶书. HPLC测定清脑口服液中人参皂昔Rgl的含量[J].中国实验方剂学杂志,2003,9(6):7-8.
[26]凌芳.高效液相色谱法测定人参提取物中Rh2的含量[J].天津理工学院学报,2003,19(l):51-53.
[27]马小琼，王龙星，徐青，等.人参皂甙的反相高效液相色谱多台阶梯度优化方法[J].高等学校化学学报,2004,25(2):238-240.
[28] Zhang Shouqin, Chen Ruizhan, Wu Hua,etal.Ginsenosideextraction from Panax quinquefolium L.(American ginseng)root by using ultrahigh pressure[J].Journal ofPharmaceutical and Biomedical Analysis,2006(41):57-63.
[29]冯育林，谢平，孙叶兵，等.中药提取工艺应用进展[J].中药材,2002,12(25):908.
[30] Zhen Du Qi, Jerz Gerold, Reiner Waibel, et al. Isolation ofdammarane saponins from Panax notoginseng by high-speedcounter-current chromatography[J].Journal of Chromatography A,2003(1008):173-180.
[31]赵文莉，张立实，贾旭东，李宁.人参皂甙抗疲劳作用的研究进展[J].中国食品卫生杂志，2008,20(5):445-448.
[32]王天成，张宏艳.人参皂甙抗心律失常作用研究进展[J].中国心脏起搏与心电生理杂志，2004,18(4):309-310.
[33] Saito H, Tsuchiya M, Naka S,et al. Effect of Panax Ginseng rooton conditioned avoidance response in rats[J].Jpn J Pharmacol,1977,(27):509-516.
[34]张均田.人参皂试Rg1和Rb1药理作用的比较[J].基础医学与临床,2000,20(5):388-390.
[35]杨吉平，赖红，方欣，等.人参皂甙Rb1对阿尔茨海默病大鼠海马结构β-淀粉样蛋白表达的影响[J].中国组织化学与细胞化学杂志,2008,17(4):301-305.
[36]方欣，杨吉平，赖红.人参皂甙Rb1对老年性痴呆模型大鼠顶叶皮质β分泌酶及早老素1表达的影响[J].解剖学杂志,2008,31(6):812-815.
[37]张明磊，杨金升，石向群，等.人参皂甙Rd对颞叶癫痫大鼠学习记忆能力及海马5-HT表达的影响[J].卒中与神经疾病,2010,17(3):147-150.
[38] CHENG Y, SHEN LH, ZHANG JT. Anti-amnestic and anti-agingeffects of ginsenoside Rg1and Rb1and its mechanism of action [J].Acta Pharmacol Sin,2005,26(2):143-149.
[39] Lee J, Choi S, Lee H, et al. Effects of g insenoside Rd anddecursinol on the neuro toxic responses induced by kainic acid inmice[J]. Planta Med,2003,69(3):230-234.
[40]朱建明.人参皂试促智作用研究进展[J].江西中医学院学报,1995,增刊:46-47。
[41]沈玲，张均田，刘态.人参增强免疫研究新进展[J].中草药,1996,27(8):499-502.
[42]张仲苗，江波，章荣华，等.人参皂甙Rg3对小鼠免疫功能的影响[J].中药药理与临床,2004,20(6):4-6.
[43]胡松华，林锋强.人参皂甙Rb1的免疫佐剂作用[J].中国兽医学报,2003,23(5):480-482.
[44]李卫平，陈敏珠.人参皂贰的免疫调节作用[J].安徽医科大学学报,1998,33(5):348-350.
[45]刘慧莲.人参皂甙的药理作用研究进展[J].潍坊学院学报,2009,9(2):106-108.
[46] Kenarova B, Neychev H, Hadjiivanova C,et al. Immunomodulatingactivity of ginsenoside Rg1from Panax ginseng[J].Jpn JPharmacol,1990(54):447-454.
[47] Yang Z, Chen A, Sun H.X, et al. Ginsenoside Rd elicits Th1andTh2immune responses to ovalbumin in mice[J]. Vaccine,2007(25):161-169.
[48]曹雪滨，黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689-691.
[49]孙晓霞，夏映红，钟国赣.人参皂甙单体Rb1对大鼠在体心脏收缩性能的影响[J].长春中医学院学报,2003,19(1):43-44.
[50]夏映红，孙晓霞，胡冰.人参皂甙单体Rb1对大鼠在体心脏收缩性能的影响[J].中国临床康复,2004,8(3):578-579.
[51]张春枝，安利佳，金凤燮.人参皂甙生理活性的研究进展[J].食品与发酵工业,2002,28(4):70-74.
[52]曹雪滨，黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689-691.
[53]王中峰，江岩，钟国赣，等.人参皂甙Rg1对培养心肌细胞钙通道阻滞作用的单通道分析[J].第三军医大学学报,1994,3:193.
[54]孙成文，赵春燕，钟国赣，等.人参二醇单体对大鼠心肌作用的单钙通道分析及ESR谱研究[J].基础医学与临床,1994,4:46.
[55]赵春燕，张文杰，钟国赣，等.人参皂甙单体Rh1对心肌作用的单钙通道分析及电子自旋共振谱研究[J].中国老年学杂志,1997,6:235.
[56]刘正湘，刘晓春.人参皂甙Rb1与Re对大鼠缺血再灌注心肌细胞凋亡的影响[J].中国组织化学与细胞化学杂志,2002,11(4):374-377.
[57]陈立波.人参皂甙对心肌缺血再灌注损伤的保护作用实验研究[J].白求恩医科大学学报,2003,10(4):553-555.
[58] Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multipleconstituents and multiple actions[J]. Biochemical Pharmacology,1999,58(11):1685-1693.
[59]夏丽娟，韩锐.人参皂甙Rh2体外对小鼠黑色素瘤细胞的分化诱导作用[J].药学学报,1996,31(10):742-745.
[60] Nakata H, Kikuchi Y, Tode T, et al. Inhibitory effects ofginsenoside Rh2on tumor growth in nude mice bearing humanovarian cancer cells[J].Japanese Journal of Cancer Research,1998,89(7):733-740.
[61] Mochizuki M, Yoo YC, Matsuzawa K, et al. Inhibitory effect oftumor metastasis in mice by saponins,ginsenoside-Rb2,20(S)and20(R)-ginsenoside-Rg3of red ginseng[J].Biological andPharmaceutical Bulletin,1995,18(9):1197-1202.
[62] Shinkai K, Akedo H, Mukai M, et al. Inhibition of in vitro tumorcell invasion by ginsenoside Rg3[J].Japanese Journal of CancerResearch,1996,87(4):357-62.
[63]陈明伟，姚昱，石志红.人参皂甙Rg3联合化疗对30例非小细胞肺癌的近期疗效观察[J].华南国防医学杂志,2005,19(1):4-6.
[64]王强，赵玲辉，杨慧科.人参皂甙Rh-2对细胞间连接黏附分子在小鼠移植瘤淋巴管表达的影响[J].解剖学研究,2007,29(1):29-32.
[65] Abe H, Arichi S, Hayashi T, et al. Ultrastructural studies of Morrishepatoma cells reversely transformed by ginsenosides[J].Experientia,1979,35(12):1647-1649.
[66] Odashima S, Nakayabu Y, Honjo N, et al. Induction of phenotypicreverse transformation by ginsenosides in cultured Morrishepatoma cells[J]. European Journal of Cancer,1979,15(6):885-892.
[67]任莉莉，魏影非，杜惠兰，等.人参抗肿瘤作用研究进展[J].Chinese Traditional Patent Medicine,2005,27(8):947-950.
[68] Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy innoninsulin-dependent diabetic patients[J]. Diabetes Care,1995(18):1373-1375.
[69] Vuksan V, Sievenpiper JL, Koo VYY, et al. American Ginseng(Panax quinquefolius L.) reduces postprandial glycemia innondiabetic subjects and subjects with type2diabetes mellitus[J].Arch Int Med,2000(160):1009-1013.
[70] Vuksan V, Sievenpiper J L, Xu Z, etal. Konjac-mannan andAmerican ginseng: emerging alternative therapies for type2diabetes mellitus[J]. J Am Coll Nutr,2001(20):370S-380S.
[71] Chung SH, Choi CG, Park SH. Comparisons between whiteginseng radix and rootlet for antidiabetic activity and mechanism inKKAY mice[J].Arch Pharm Res,2001(24):214–218.
[72]杨明，崔志勇，王岩.人参多糖降血糖和肝糖原作用的研究[J].中药药理与临床,1991,7(5):22-24.
[73]杨明，崔志勇，王岩.人参多糖对动物正常血糖及各种实验性高血糖的影响[J].中国中药杂志,1992,17(8):500-501.
[74] Shen YJ. Pharmacology of Traditional Chinese Medicine[J].Beijing, China. Renmin Weisheng Press,2000.102-106.
[75]李广，李浩波，刘璐，等.皂甙的生理活性及其应用研究进展[J].中国农学学报,2003(12):3-6.
[76]李丽艳.人参皂甙的最新研究进展[J].四川省卫生管理干部学院学报,2004,23(4):293-295.
[77]张勤，叶再元，杜卫东.人参皂甙对腹腔感染大鼠血清白蛋白及白介素-6影响的实验研究[J].浙江中医学院学报,2003,27(4):66.
[78]林一萍，吴瑞.人参茶多酚等在体外抗含氧自由基的分析[J].福建省中医学院学报.1995.5(3):27.
[79]谢业琪，李秋萍，张芝贤，等.西洋参分离成份——原人参二醇三醇皂甙某些生理作用的实验研究[J].沈阳体育学院学报,2001,1(1):5-9.
[80]田生礼，冯彪.人参多糖对X射线小鼠脾脏自由基含量的影响[J].辐射研究与辐射工艺学报.1995,13(4):11.
[81]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[J].解剖科学进展.2000,6(3):264-266.
[82]梅兵，王耀发，吴骏晞，等.氧自由基致体外培养血管内皮细胞的损伤及人参皂甙的保护作用[J].药学学报.1994,29(11):801-808.
[83]赵萍，王晓明，孙成文，等.齐墩果酸人参皂甙Ro对心肌细胞——单钙通道活动与自由基含量的影响[J].白求恩医科大学学报,1994,20(5):540-542.\
[84]赵翌.20-(R)-人参皂甙Rg3抗肿瘤作用的研究进展[J].临床肿瘤学杂志2001,6(l):81-82
[85]包文芳，李保桦.西洋参药理作用的研究进展[J].天然产物研究与开发,1998,10(3):103-108
[86]薛东波.人参皂甙Rg3抗肿瘤转移作用的研究进展[J].中国中西医结合外科杂志,2001,7(4):289-290.
[87] Allen AR. Surgery of experimental lesion of spinal cord equivalentto crush injury of fracture dislocation of spinal column: preliminaryreport. JAMA.1911,57:878.
[88] Dumont RJ, Okonkwo DO, Verma S, et al. Acute spinal cord injury,part I: Pathophysiologic mechanisms. Clin Neuropharmacol,2001,24(5):254-264.
[89]马玉羡.脑缺血再灌注损伤病理生理机制研究进展[J].河南医学研究,1998,7(4):375-378.
[90] Hegstad E, Berg-Johnsen J, Langmoen IA. Failure of allopurinol toprotect against cerebral injury when given after the start ofhypoxia[J]. Acta Neurol Scand,1991,83(5):286-288.
[91] Hwang J1, Huh J, Kim J, Jeon Y, Cho S, Han S. Pretreatment witherythropoietin attenuates the neurological injury after spinal cordischemia[J]. Spinal Cord,2012,50(3):208-212.
[92] Hwang J, Kim J, Park S, et al. Magnesium sulfate does not protectspinal cord against ischemic injury[J]. J Invest Surg,2011,24(6):250-256.
[93] Nakamichi T, Kawada S. Glutamate neurotoxicity during spinalcordischemia-development of a delayed-onsetparaplegiamodel[J].Nippon Kyobu GekaGakkai Zassh,2010,45(10):1667-1673.
[94] Elizabeth Finkel. The Mitochondrion: Is It Central toApoptosis?[J].Science,2001,292(5517):624-626.
[95] PeasleyMA,Shi R.Ischemic insult exacerbates acrolein-inducedconduction loss and axonal membrane disruption in guinea pigspinal cordwhite matter[J].J Neurol Sci,2003,216(1):23-32.
[96] Shaafi S, Afrooz MR, Hajipour B, et al. Anti-oxidative effect oflipoic Acid in spinal cord ischemia/reperfusion[J].Med Princ Pract,2011,20(1):19-22.
[97] Sommer C, Roth SU, Kuhn R, et al. Metabotropic glutamatereceptor subtypes are differentially expressed after transientcerebral ischemia without, during and after tolerance induction inthe gerbil hippocampus [J]. Brain Res,2000,872(1-2):172-180.
[98] Sonkar SK, Gupta A, Atam V, et al. Clinical profile of neurologicalmanifestation in human immunodeficiency virus-positive patients[J]. N Am J Med Sci,2012,11:596-599.
[99] Sung B, Wang S, Zhou B, et al. Altered spinal arachidonic acidturnover after peripheral nerve injury regulates regional glutamateconcentration and neuropathic pain behaviors in rats [J]. Pain,2007.131(1-2):121-131.
[100]韩济生.神经科学原理[M].2版,北京:北京医科大学出版社,1993:524-538.
[101] Amar AP, Levy ML. Pathogenesis and pharmacologicalstrategies for mitigating secondary damage in acute spinal cordinjury[J].Neurosurgery,1999,44:1027-1040.
[102] Li S, Stys PK. Mechanisms of ionotropic glutamatereceptor-mediated excitotoxicity in isolated spinal cord whitematter[J].J Neurosci,2000,20(3):1190-1198.
[103] Matsushita Y, Shima K, Nawashiro H, et al. Real timemonitoring of glutamate following fluid percussion brian injurywith hypox in the rat[J].J Neurotrauma,2000,17:143-153.
[104] Karadottir R, Cavelier P, Bergersen LH, et al. NMDA receptorsare expressed in oligodendrocytes and activated inischaemia[J].Nature,2005,438:1162-1166.
[105] McCulough J L, Holier LH, Nugent M. Paraplegia after thoracicaortic occlusion: influence of cerebrospinal fluid drainage.Experimental and early clinical results[J].J Vasc Surg,1988,7(1):153-158.
[106] Liao SL1, Chen WY, Raung SL, Kuo JS, Chen CJ. Association ofimmune responses and ischemic brain infarction in rat[J].Neuroreport,2001,12(9):1943-1947.
[107] Michael tymianski, charles H. Normal and abnormal calciumhomeostasis in neurons: A basis for the pathophysiologyof traumatic and ischemic central nervous system injury[J].Neurosurgery,1996,38(6):1176-1195.
[108] Zurita M, Vaquero J, Zurita I. Presence and significance ofCD-95(Fas/APO1) expression after spinal cord injury[J].JNeurosurg,2001,94(2):257-264.
[109] Rybnikova E, Tulkova E, Pelto-Huikko M, et al. Mildpreconditioning hypoxia modifies nerve growth factor-inducedgene A messenger RNA expression in the rat brain induced severebypoxia [J].Neurosci Lett,2002,329(1):49-52.
[110]管华清，顾晓晖，杨惠林等.热休克蛋白对脊髓缺血再灌注损伤的保护作用[J].脊柱外科杂志,2004,2(6):363-366。
[111]王强，熊利泽，陈绍洋等.川芎嗪对兔脊髓缺血/再灌注损伤的保护作用和治疗作用[J].中华麻醉学杂志,2001,21(3):163-166.
[112] Perry VH. Gordon, S. Macrophages and microglia in the nervoussystem[J].Trends Neurosci,1988,11:273–277.
[113] Logan MP, Parker S, Shi R. Glutathione and ascorbic acidenhance recovery of Guinea pig spinal cord white matter followingischemia and acrolein exposure[J].Pathobiology,2005,72(4):171-178.
[114]杨小玉，朱庆三，赵立君，等.脊髓缺血-再灌注损伤细胞间粘附分子-1及白细胞介素-1的表达[J].中国脊柱脊髓杂志,2004,14(3):167-170.
[115] Wakamatsu H. The effect of moderate hypothermia andintrathecaldialysite and neurological and histopathologicaloutcome in transient spinal cord ischemia in rabbits[J].AnerthAnalg,1999,88(1):56-60.
[116]蒙革，朱朗标，余其飞，等。缺血预处理对脊髓缺血兔后肢神经功能的影响[J].中华老年心血管病杂志,2000,2(3):192-195.
[117] Boulares AH，Ren T．Mechanism of Acetaminophen-InducedApoptosis in Cultured Cells: Roles of Caspase-3, DNAFragmentation Factor, and the Ca2+and Mg2+EndonucleaseDNAS1L3[J].Pharmacol Toxicol,2004,94(1):19.
[118] Perlman JI, McCole SM, Pulluru P, et al. Disturbances in thedistribution of neurotransmitters in the rat retina after ischemia[J].Curr Eye Res,1996,15(6):589-596.
[119]张晓娟，郭莲军，曲玲，等.蝙蝠葛酚性碱对大鼠局灶性脑缺血-再灌注继发炎性损伤的保护作用[J].药学学报,2004,39(8):661-665.
[120] Piao CS, Kim JB, Han PL, Lee JK. Administration of the p38MAPK inhibitor SB203580affords brain protection with a widetherapeutic window against focal ischemic insult[J].J Neurosci Res,2003,73(4):537-544.
[121]吕纪华，贺敏，黄建春，等.玉郎伞黄酮对心肌缺血再灌注损伤心肌组织ATP酶和凋亡蛋白的影响[J].中国实验方剂学杂志,2010,16(13):162.
[122] Gottlieb RA, Burleson KO, Kloner RA, et al. Reperfusion injuryinduces apoptosis in rabbit cardiomyocytes[J].J Clin Invest,1994,94(4):1621-1628.
[123] Wolfrum S, Richardt G, Dominiak P, et al. Apstatin, a selectiveinhibitor of aminopeptidase P, reduces myocardial infarct size by akinin-dependent pathway[J]. Br J Pharmacol,2001,134(2):370-374.
[124] Yamaguchi K, Kawahara T, Kumakura S, et al. Effect of olprinone,a phosphodiesterase III inhibitor, on hepatic ischemia-reperfusioninjury in rats[J]. hock.2010,33(4):436-441.
[125] Ben DF, Yu XY, Ji GY, et al. TLR4mediates lung injury andinflammation in intestinal ischemia-reperfusion[J].J Surg Res,2012,174(2):326-333.
[126]孙新平，杨旭凯，程彦斌.缺血预处理对急性肾缺血再灌注细胞凋亡及ET-1表达的影响[J].西北国防医学杂志,2009,30(3):202-204.
[127]郭来敬，张志仁，陈东辉，等.电子顺磁共振检测心肌缺血再灌产生的氧自由基及其保护的实验研究[J].心肺血管病杂志，2000，19(1)：58-61.
[128]马国强.心肌缺血/再灌注损伤与细胞凋亡的机制及其防治研究进展[J].滨州医学院学报，2007，3(1)：50-52.
[129] PCHEJETSKI D,KUNDUZOVA O,DAYON A,et al.Oxidativestress-dependent sphingosine kinase-1inhibition mediatesmonoamine oxidase A-associated cardiac cell apoptosis[J].Circ Res,2007,100(1):41-49.
[130] Salas MA, Valverde CA. Sánchez G, et al. The signalling pathwayof CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury[J].J Mol Cell Cardiol,2010,48(6):1298.
[131]黄飞，李亚男，尹飞，等.人参皂甙Rb1减轻大鼠脊髓缺血再灌注损伤的实验研究[J].脊柱外科杂志,2013,11(3):173-177.
[132] Wang HY, Qi LW, Wang CZ, et al. Bioactivity enhancement ofherbal supplements by intestinal microbiota focusing on ginseno-sides[J]. Am J Chin Med,2011,39(6):1103-1115.
[133] Perry E, Howes MJ. Medicinal plants and dementia therapy:herbal hopes for brain aging?[J].CNS Neurosci Ther,2011,17(6):683-698.
[134]高小青，杜杰，邓莉，等.人参皂甙Rb1对大鼠脑缺血再灌注后巢蛋白表达的影响[J].现代医药卫生,2011,27(2):161-163.
[135]杨进国，夏中元，赵博，等.人参皂甙Rb1在核因子NF-E2相关因子2/血红素氧合酶-1通路减轻肠缺血再灌注致急性肺损伤中的分子机制[J].中华实验外科杂志,2012,29(11):2234-2236.
[136]耿庆，乌达，谢远财，等.人参皂甙Rb1对肺缺血再灌注损伤细胞凋亡及其调控基因表达的影响[J].中国中西医结合急救杂志,2005,12(3):159-161.
[137] Wu Y, Xia ZY, Dou J, Zhang L, et al. Protective effect ofginsenoside Rb1against myocardial ischemia/reperfusion injury instreptozotocin-induced diabetic rats[J].Mol Biol Rep,2011,38(7):4327-4335.
[138]盘强文，冉兵，冯志强，等.人参二醇组皂甙促进受损的培养肾小管细胞增殖的作用及机制研究[J].中国中西医结合急救杂志,2003,10(3):142-145.
[139] Kiefer D, Pantuso T. Panax ginseng[J]. Am Fam Physician.2003,15,68(8):1539-1542.
[140] YANG Shu-long, FENG Zhi-qiang, WU Li-sha. Shenfu injectionprevents kidney from acute ischemia-reperfusion injury inrabbits[J]. Chinese Journal of Pathophysiology,2003,19(3):353-356.
[141]曾庆华，战术，张文杰，等.人参皂甙单体Rb1对豚鼠心肌细胞ICa2+电流阻滞作用的研究[J].白求恩医科大学学报,1997,23(3):265-267.
[142]黄晓光，邵珊，李荣山.人参皂甙Rb1对大鼠急性肾小管损伤的保护作用[J].临床医药实践杂志,2006,15(8):579-581.
[143] Li YK, Chen XC, Zhu YG, et al. Ginsenoside Rb1attenuatesokadaic acid-induced Tau protein hyperphosphorylation in rathippocampal neurons[J]. Sheng Li Xue Bao.2005,57(2):154-160.
[144] Attele AS, Zhou YP, Xie JT, et al. Antidiabetic effects of Panaxginseng berry extract and the identification of an effectivecomponent[J]. Diabetes,2002,51(6):1851-1858.
[145] Yuan QL, Yang CX, Xu P, et al. Neuroprotective effects ofginsenoside Rb1on transient cerebral ischemia in rats[J].Brain Res,2007,1167:1-12.
[146] Ji YC, Kim YB, Park SW, et al. Neuroprotective effect of ginsengtotal saponins in experimental traumatic brain injury[J]. J KoreanMed Sci,2005,20(2):291-296.
[147][147]Yoshikawa T, Akiyoshi Y, Susumu T, et al. Ginsenoside Rb1reduces neurodegeneration in the peri-infarct area of athromboembolic stroke model in non-human primates[J].JPharmacol Sci,2008,107(1):32-40.
[148]李君庆，张香阁，张均田.人参皂甙Rg1抗神经细胞凋亡作用机制的研究[J].药学学报,1997,32(6):406-410.
[149]朱陵群，范吉平，黄放福.人参皂甙Rb1对大鼠胎鼠海马神经细胞凋亡的影响[J].中国病理生理杂志.2001,17(12):1229-1231.
[150]聂荣庆，李扣华，胡国柱等.人参皂甙Rb1抗新生大鼠大脑皮层神经细胞缺氧性凋亡研究[J].中国康复理论与实践.2004,10(12):723-725.
[151]陈晓春，朱元贵，王小众，等.人参皂甙Rg1对PC12细胞凋亡保护作用的可能机制[J].药学学报,2001,36(6):411-414.
[152] Cosulich S C, Worrall V, Hedge PJ, et al. Regulation of apoptosisby BH3domains in a cell-free system[J]. Curr Biol,1997,7:913-920.
[153]郭若霖，万晓华，陈晓建.人参皂甙Rg1和Rb1对脐血CD34＋细胞凋亡的影响[J].华现代临床医学杂志,2004,2(4):385-387.
[2]张树臣主编,中国人参[M].上海:上海科技教育出版社,1992.
[3]丛登立，宋长春，徐景达.西洋参叶中20(S)-人参皂试-Rh4，Rh2和人参皂试-Rh3的分离与鉴定[J].中国药学杂志.2000,35(2):82-84.
[4]王本祥.人参的研究[M].天津：天津科学技术出版社，1988.3-4.
[5]窦德强，任杰，陈颖，等.商品人参根的化学成分研究[J].中国中药杂志,2003,28(6):522-524.
[6]姚新生，徐馁绪，陈英杰.人参成分的研究[J].中国药学年鉴,1991,23-25.
[7]姚新生.天然药物化学[M].北京：人民卫生出版社，1990.
[8]窦德强，靳玲，陈英杰.人参的化学成分及药理活性的研究进展与展望[J].沈阳药科大学学报,1999,16(2):151-156.
[9]杨云，冯卫生主编.中药化学成分提取分离手册[M].中国中医药出版社,1998:2.
[10] Dou DQ, Chen YJ, Liang LH, et al. Six New Dammarance-typeTriteprene Saponions from the levaes of Panxa ginseng.ChemPharmbull.2001,49(4):442-445.
[11]张春枝，安利佳，等.人参皂试生理活性的研究进展[J].食品与发酵工业,2003,28(4):70-74.
[12] Nicola Fuzzati. Analysis methods of ginsenosides[J]. Journal ofChromatography B,2004(812):119-133.
[13]朱丹妮，杨力，严永清.西洋参与人参中人参皂甙含量的比较.植物资源与环学报.2000,9(3):1-4.
[14]窦得强，靳玲，陈英杰.人参的化学成分及药理活性的研究进展与展望[J].沈阳药科大学学报,1999,16(2):151-156.
[15]王本详.人参研究进展[M].天津:天津科学技术出版社,1991.
[16]王铁生，常维春，尚培根，等.中国人参[M].辽宁：辽宁科学技术出版社,2001,677-679.
[17]杨玉琪，李玛琳.人参皂甙的抗肿瘤作用及其机制[J].药学进展,2003,27(5):287-290.
[18]张玲，单卫华，梁瑞雪，等.人参提取工艺研究[J].时珍国医国药,2000,11(9):777-779.
[19]吴正中，周国明，谢玉琼.正交试验法提取人参皂甙工艺的研究[J].中国药房,2003,27(5):287-290.
[20]张崇禧，郑友兰，张春红，等.大孔树脂吸附人参总皂成工艺及再生使用的研究[J].中国药学杂志,2003,38(9):661-664.
[21]]S.Youn Yuen, K. Ming Yu, C. Yuan Shim. Microwave-assistedextraction of ginsenosides from ginseng root[J].MicrochemicalJournal,2003,74(2):131-139.
[22]张镜澄.超临界流体萃取[M].北京:化学工业出版社,2000,102-123.
[23]高巨.树脂法提取三七叶皂甙及三七皂甙组分分离的研究[D].天津：南开大学高分子化学与物理,2005.
[24]朱萱萱，茅泳雯，何润霞，等.反相HPLC法测定药用人参中多种人参皂甙的含量[J].中国生化药物杂志,1998,19(1):28-31.
[25]王隶书. HPLC测定清脑口服液中人参皂昔Rgl的含量[J].中国实验方剂学杂志,2003,9(6):7-8.
[26]凌芳.高效液相色谱法测定人参提取物中Rh2的含量[J].天津理工学院学报,2003,19(l):51-53.
[27]马小琼，王龙星，徐青，等.人参皂甙的反相高效液相色谱多台阶梯度优化方法[J].高等学校化学学报,2004,25(2):238-240.
[28] Zhang Shouqin, Chen Ruizhan, Wu Hua,etal.Ginsenosideextraction from Panax quinquefolium L.(American ginseng)root by using ultrahigh pressure[J].Journal ofPharmaceutical and Biomedical Analysis,2006(41):57-63.
[29]冯育林，谢平，孙叶兵，等.中药提取工艺应用进展[J].中药材,2002,12(25):908.
[30] Zhen Du Qi, Jerz Gerold, Reiner Waibel, et al. Isolation ofdammarane saponins from Panax notoginseng by high-speedcounter-current chromatography[J].Journal of Chromatography A,2003(1008):173-180.
[31]赵文莉，张立实，贾旭东，李宁.人参皂甙抗疲劳作用的研究进展[J].中国食品卫生杂志，2008,20(5):445-448.
[32]王天成，张宏艳.人参皂甙抗心律失常作用研究进展[J].中国心脏起搏与心电生理杂志，2004,18(4):309-310.
[33] Saito H, Tsuchiya M, Naka S,et al. Effect of Panax Ginseng rooton conditioned avoidance response in rats[J].Jpn J Pharmacol,1977,(27):509-516.
[34]张均田.人参皂试Rg1和Rb1药理作用的比较[J].基础医学与临床,2000,20(5):388-390.
[35]杨吉平，赖红，方欣，等.人参皂甙Rb1对阿尔茨海默病大鼠海马结构β-淀粉样蛋白表达的影响[J].中国组织化学与细胞化学杂志,2008,17(4):301-305.
[36]方欣，杨吉平，赖红.人参皂甙Rb1对老年性痴呆模型大鼠顶叶皮质β分泌酶及早老素1表达的影响[J].解剖学杂志,2008,31(6):812-815.
[37]张明磊，杨金升，石向群，等.人参皂甙Rd对颞叶癫痫大鼠学习记忆能力及海马5-HT表达的影响[J].卒中与神经疾病,2010,17(3):147-150.
[38] CHENG Y, SHEN LH, ZHANG JT. Anti-amnestic and anti-agingeffects of ginsenoside Rg1and Rb1and its mechanism of action [J].Acta Pharmacol Sin,2005,26(2):143-149.
[39] Lee J, Choi S, Lee H, et al. Effects of g insenoside Rd anddecursinol on the neuro toxic responses induced by kainic acid inmice[J]. Planta Med,2003,69(3):230-234.
[40]朱建明.人参皂试促智作用研究进展[J].江西中医学院学报,1995,增刊:46-47。
[41]沈玲，张均田，刘态.人参增强免疫研究新进展[J].中草药,1996,27(8):499-502.
[42]张仲苗，江波，章荣华，等.人参皂甙Rg3对小鼠免疫功能的影响[J].中药药理与临床,2004,20(6):4-6.
[43]胡松华，林锋强.人参皂甙Rb1的免疫佐剂作用[J].中国兽医学报,2003,23(5):480-482.
[44]李卫平，陈敏珠.人参皂贰的免疫调节作用[J].安徽医科大学学报,1998,33(5):348-350.
[45]刘慧莲.人参皂甙的药理作用研究进展[J].潍坊学院学报,2009,9(2):106-108.
[46] Kenarova B, Neychev H, Hadjiivanova C,et al. Immunomodulatingactivity of ginsenoside Rg1from Panax ginseng[J].Jpn JPharmacol,1990(54):447-454.
[47] Yang Z, Chen A, Sun H.X, et al. Ginsenoside Rd elicits Th1andTh2immune responses to ovalbumin in mice[J]. Vaccine,2007(25):161-169.
[48]曹雪滨，黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689-691.
[49]孙晓霞，夏映红，钟国赣.人参皂甙单体Rb1对大鼠在体心脏收缩性能的影响[J].长春中医学院学报,2003,19(1):43-44.
[50]夏映红，孙晓霞，胡冰.人参皂甙单体Rb1对大鼠在体心脏收缩性能的影响[J].中国临床康复,2004,8(3):578-579.
[51]张春枝，安利佳，金凤燮.人参皂甙生理活性的研究进展[J].食品与发酵工业,2002,28(4):70-74.
[52]曹雪滨，黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689-691.
[53]王中峰，江岩，钟国赣，等.人参皂甙Rg1对培养心肌细胞钙通道阻滞作用的单通道分析[J].第三军医大学学报,1994,3:193.
[54]孙成文，赵春燕，钟国赣，等.人参二醇单体对大鼠心肌作用的单钙通道分析及ESR谱研究[J].基础医学与临床,1994,4:46.
[55]赵春燕，张文杰，钟国赣，等.人参皂甙单体Rh1对心肌作用的单钙通道分析及电子自旋共振谱研究[J].中国老年学杂志,1997,6:235.
[56]刘正湘，刘晓春.人参皂甙Rb1与Re对大鼠缺血再灌注心肌细胞凋亡的影响[J].中国组织化学与细胞化学杂志,2002,11(4):374-377.
[57]陈立波.人参皂甙对心肌缺血再灌注损伤的保护作用实验研究[J].白求恩医科大学学报,2003,10(4):553-555.
[58] Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multipleconstituents and multiple actions[J]. Biochemical Pharmacology,1999,58(11):1685-1693.
[59]夏丽娟，韩锐.人参皂甙Rh2体外对小鼠黑色素瘤细胞的分化诱导作用[J].药学学报,1996,31(10):742-745.
[60] Nakata H, Kikuchi Y, Tode T, et al. Inhibitory effects ofginsenoside Rh2on tumor growth in nude mice bearing humanovarian cancer cells[J].Japanese Journal of Cancer Research,1998,89(7):733-740.
[61] Mochizuki M, Yoo YC, Matsuzawa K, et al. Inhibitory effect oftumor metastasis in mice by saponins,ginsenoside-Rb2,20(S)and20(R)-ginsenoside-Rg3of red ginseng[J].Biological andPharmaceutical Bulletin,1995,18(9):1197-1202.
[62] Shinkai K, Akedo H, Mukai M, et al. Inhibition of in vitro tumorcell invasion by ginsenoside Rg3[J].Japanese Journal of CancerResearch,1996,87(4):357-62.
[63]陈明伟，姚昱，石志红.人参皂甙Rg3联合化疗对30例非小细胞肺癌的近期疗效观察[J].华南国防医学杂志,2005,19(1):4-6.
[64]王强，赵玲辉，杨慧科.人参皂甙Rh-2对细胞间连接黏附分子在小鼠移植瘤淋巴管表达的影响[J].解剖学研究,2007,29(1):29-32.
[65] Abe H, Arichi S, Hayashi T, et al. Ultrastructural studies of Morrishepatoma cells reversely transformed by ginsenosides[J].Experientia,1979,35(12):1647-1649.
[66] Odashima S, Nakayabu Y, Honjo N, et al. Induction of phenotypicreverse transformation by ginsenosides in cultured Morrishepatoma cells[J]. European Journal of Cancer,1979,15(6):885-892.
[67]任莉莉，魏影非，杜惠兰，等.人参抗肿瘤作用研究进展[J].Chinese Traditional Patent Medicine,2005,27(8):947-950.
[68] Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy innoninsulin-dependent diabetic patients[J]. Diabetes Care,1995(18):1373-1375.
[69] Vuksan V, Sievenpiper JL, Koo VYY, et al. American Ginseng(Panax quinquefolius L.) reduces postprandial glycemia innondiabetic subjects and subjects with type2diabetes mellitus[J].Arch Int Med,2000(160):1009-1013.
[70] Vuksan V, Sievenpiper J L, Xu Z, etal. Konjac-mannan andAmerican ginseng: emerging alternative therapies for type2diabetes mellitus[J]. J Am Coll Nutr,2001(20):370S-380S.
[71] Chung SH, Choi CG, Park SH. Comparisons between whiteginseng radix and rootlet for antidiabetic activity and mechanism inKKAY mice[J].Arch Pharm Res,2001(24):214–218.
[72]杨明，崔志勇，王岩.人参多糖降血糖和肝糖原作用的研究[J].中药药理与临床,1991,7(5):22-24.
[73]杨明，崔志勇，王岩.人参多糖对动物正常血糖及各种实验性高血糖的影响[J].中国中药杂志,1992,17(8):500-501.
[74] Shen YJ. Pharmacology of Traditional Chinese Medicine[J].Beijing, China. Renmin Weisheng Press,2000.102-106.
[75]李广，李浩波，刘璐，等.皂甙的生理活性及其应用研究进展[J].中国农学学报,2003(12):3-6.
[76]李丽艳.人参皂甙的最新研究进展[J].四川省卫生管理干部学院学报,2004,23(4):293-295.
[77]张勤，叶再元，杜卫东.人参皂甙对腹腔感染大鼠血清白蛋白及白介素-6影响的实验研究[J].浙江中医学院学报,2003,27(4):66.
[78]林一萍，吴瑞.人参茶多酚等在体外抗含氧自由基的分析[J].福建省中医学院学报.1995.5(3):27.
[79]谢业琪，李秋萍，张芝贤，等.西洋参分离成份——原人参二醇三醇皂甙某些生理作用的实验研究[J].沈阳体育学院学报,2001,1(1):5-9.
[80]田生礼，冯彪.人参多糖对X射线小鼠脾脏自由基含量的影响[J].辐射研究与辐射工艺学报.1995,13(4):11.
[81]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[J].解剖科学进展.2000,6(3):264-266.
[82]梅兵，王耀发，吴骏晞，等.氧自由基致体外培养血管内皮细胞的损伤及人参皂甙的保护作用[J].药学学报.1994,29(11):801-808.
[83]赵萍，王晓明，孙成文，等.齐墩果酸人参皂甙Ro对心肌细胞——单钙通道活动与自由基含量的影响[J].白求恩医科大学学报,1994,20(5):540-542.\
[84]赵翌.20-(R)-人参皂甙Rg3抗肿瘤作用的研究进展[J].临床肿瘤学杂志2001,6(l):81-82
[85]包文芳，李保桦.西洋参药理作用的研究进展[J].天然产物研究与开发,1998,10(3):103-108
[86]薛东波.人参皂甙Rg3抗肿瘤转移作用的研究进展[J].中国中西医结合外科杂志,2001,7(4):289-290.
[87] Allen AR. Surgery of experimental lesion of spinal cord equivalentto crush injury of fracture dislocation of spinal column: preliminaryreport. JAMA.1911,57:878.
[88] Dumont RJ, Okonkwo DO, Verma S, et al. Acute spinal cord injury,part I: Pathophysiologic mechanisms. Clin Neuropharmacol,2001,24(5):254-264.
[89]马玉羡.脑缺血再灌注损伤病理生理机制研究进展[J].河南医学研究,1998,7(4):375-378.
[90] Hegstad E, Berg-Johnsen J, Langmoen IA. Failure of allopurinol toprotect against cerebral injury when given after the start ofhypoxia[J]. Acta Neurol Scand,1991,83(5):286-288.
[91] Hwang J1, Huh J, Kim J, Jeon Y, Cho S, Han S. Pretreatment witherythropoietin attenuates the neurological injury after spinal cordischemia[J]. Spinal Cord,2012,50(3):208-212.
[92] Hwang J, Kim J, Park S, et al. Magnesium sulfate does not protectspinal cord against ischemic injury[J]. J Invest Surg,2011,24(6):250-256.
[93] Nakamichi T, Kawada S. Glutamate neurotoxicity during spinalcordischemia-development of a delayed-onsetparaplegiamodel[J].Nippon Kyobu GekaGakkai Zassh,2010,45(10):1667-1673.
[94] Elizabeth Finkel. The Mitochondrion: Is It Central toApoptosis?[J].Science,2001,292(5517):624-626.
[95] PeasleyMA,Shi R.Ischemic insult exacerbates acrolein-inducedconduction loss and axonal membrane disruption in guinea pigspinal cordwhite matter[J].J Neurol Sci,2003,216(1):23-32.
[96] Shaafi S, Afrooz MR, Hajipour B, et al. Anti-oxidative effect oflipoic Acid in spinal cord ischemia/reperfusion[J].Med Princ Pract,2011,20(1):19-22.
[97] Sommer C, Roth SU, Kuhn R, et al. Metabotropic glutamatereceptor subtypes are differentially expressed after transientcerebral ischemia without, during and after tolerance induction inthe gerbil hippocampus [J]. Brain Res,2000,872(1-2):172-180.
[98] Sonkar SK, Gupta A, Atam V, et al. Clinical profile of neurologicalmanifestation in human immunodeficiency virus-positive patients[J]. N Am J Med Sci,2012,11:596-599.
[99] Sung B, Wang S, Zhou B, et al. Altered spinal arachidonic acidturnover after peripheral nerve injury regulates regional glutamateconcentration and neuropathic pain behaviors in rats [J]. Pain,2007.131(1-2):121-131.
[100]韩济生.神经科学原理[M].2版,北京:北京医科大学出版社,1993:524-538.
[101] Amar AP, Levy ML. Pathogenesis and pharmacologicalstrategies for mitigating secondary damage in acute spinal cordinjury[J].Neurosurgery,1999,44:1027-1040.
[102] Li S, Stys PK. Mechanisms of ionotropic glutamatereceptor-mediated excitotoxicity in isolated spinal cord whitematter[J].J Neurosci,2000,20(3):1190-1198.
[103] Matsushita Y, Shima K, Nawashiro H, et al. Real timemonitoring of glutamate following fluid percussion brian injurywith hypox in the rat[J].J Neurotrauma,2000,17:143-153.
[104] Karadottir R, Cavelier P, Bergersen LH, et al. NMDA receptorsare expressed in oligodendrocytes and activated inischaemia[J].Nature,2005,438:1162-1166.
[105] McCulough J L, Holier LH, Nugent M. Paraplegia after thoracicaortic occlusion: influence of cerebrospinal fluid drainage.Experimental and early clinical results[J].J Vasc Surg,1988,7(1):153-158.
[106] Liao SL1, Chen WY, Raung SL, Kuo JS, Chen CJ. Association ofimmune responses and ischemic brain infarction in rat[J].Neuroreport,2001,12(9):1943-1947.
[107] Michael tymianski, charles H. Normal and abnormal calciumhomeostasis in neurons: A basis for the pathophysiologyof traumatic and ischemic central nervous system injury[J].Neurosurgery,1996,38(6):1176-1195.
[108] Zurita M, Vaquero J, Zurita I. Presence and significance ofCD-95(Fas/APO1) expression after spinal cord injury[J].JNeurosurg,2001,94(2):257-264.
[109] Rybnikova E, Tulkova E, Pelto-Huikko M, et al. Mildpreconditioning hypoxia modifies nerve growth factor-inducedgene A messenger RNA expression in the rat brain induced severebypoxia [J].Neurosci Lett,2002,329(1):49-52.
[110]管华清，顾晓晖，杨惠林等.热休克蛋白对脊髓缺血再灌注损伤的保护作用[J].脊柱外科杂志,2004,2(6):363-366。
[111]王强，熊利泽，陈绍洋等.川芎嗪对兔脊髓缺血/再灌注损伤的保护作用和治疗作用[J].中华麻醉学杂志,2001,21(3):163-166.
[112] Perry VH. Gordon, S. Macrophages and microglia in the nervoussystem[J].Trends Neurosci,1988,11:273–277.
[113] Logan MP, Parker S, Shi R. Glutathione and ascorbic acidenhance recovery of Guinea pig spinal cord white matter followingischemia and acrolein exposure[J].Pathobiology,2005,72(4):171-178.
[114]杨小玉，朱庆三，赵立君，等.脊髓缺血-再灌注损伤细胞间粘附分子-1及白细胞介素-1的表达[J].中国脊柱脊髓杂志,2004,14(3):167-170.
[115] Wakamatsu H. The effect of moderate hypothermia andintrathecaldialysite and neurological and histopathologicaloutcome in transient spinal cord ischemia in rabbits[J].AnerthAnalg,1999,88(1):56-60.
[116]蒙革，朱朗标，余其飞，等。缺血预处理对脊髓缺血兔后肢神经功能的影响[J].中华老年心血管病杂志,2000,2(3):192-195.
[117] Boulares AH，Ren T．Mechanism of Acetaminophen-InducedApoptosis in Cultured Cells: Roles of Caspase-3, DNAFragmentation Factor, and the Ca2+and Mg2+EndonucleaseDNAS1L3[J].Pharmacol Toxicol,2004,94(1):19.
[118] Perlman JI, McCole SM, Pulluru P, et al. Disturbances in thedistribution of neurotransmitters in the rat retina after ischemia[J].Curr Eye Res,1996,15(6):589-596.
[119]张晓娟，郭莲军，曲玲，等.蝙蝠葛酚性碱对大鼠局灶性脑缺血-再灌注继发炎性损伤的保护作用[J].药学学报,2004,39(8):661-665.
[120] Piao CS, Kim JB, Han PL, Lee JK. Administration of the p38MAPK inhibitor SB203580affords brain protection with a widetherapeutic window against focal ischemic insult[J].J Neurosci Res,2003,73(4):537-544.
[121]吕纪华，贺敏，黄建春，等.玉郎伞黄酮对心肌缺血再灌注损伤心肌组织ATP酶和凋亡蛋白的影响[J].中国实验方剂学杂志,2010,16(13):162.
[122] Gottlieb RA, Burleson KO, Kloner RA, et al. Reperfusion injuryinduces apoptosis in rabbit cardiomyocytes[J].J Clin Invest,1994,94(4):1621-1628.
[123] Wolfrum S, Richardt G, Dominiak P, et al. Apstatin, a selectiveinhibitor of aminopeptidase P, reduces myocardial infarct size by akinin-dependent pathway[J]. Br J Pharmacol,2001,134(2):370-374.
[124] Yamaguchi K, Kawahara T, Kumakura S, et al. Effect of olprinone,a phosphodiesterase III inhibitor, on hepatic ischemia-reperfusioninjury in rats[J]. hock.2010,33(4):436-441.
[125] Ben DF, Yu XY, Ji GY, et al. TLR4mediates lung injury andinflammation in intestinal ischemia-reperfusion[J].J Surg Res,2012,174(2):326-333.
[126]孙新平，杨旭凯，程彦斌.缺血预处理对急性肾缺血再灌注细胞凋亡及ET-1表达的影响[J].西北国防医学杂志,2009,30(3):202-204.
[127]郭来敬，张志仁，陈东辉，等.电子顺磁共振检测心肌缺血再灌产生的氧自由基及其保护的实验研究[J].心肺血管病杂志，2000，19(1)：58-61.
[128]马国强.心肌缺血/再灌注损伤与细胞凋亡的机制及其防治研究进展[J].滨州医学院学报，2007，3(1)：50-52.
[129] PCHEJETSKI D,KUNDUZOVA O,DAYON A,et al.Oxidativestress-dependent sphingosine kinase-1inhibition mediatesmonoamine oxidase A-associated cardiac cell apoptosis[J].Circ Res,2007,100(1):41-49.
[130] Salas MA, Valverde CA. Sánchez G, et al. The signalling pathwayof CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury[J].J Mol Cell Cardiol,2010,48(6):1298.
[131]黄飞，李亚男，尹飞，等.人参皂甙Rb1减轻大鼠脊髓缺血再灌注损伤的实验研究[J].脊柱外科杂志,2013,11(3):173-177.
[132] Wang HY, Qi LW, Wang CZ, et al. Bioactivity enhancement ofherbal supplements by intestinal microbiota focusing on ginseno-sides[J]. Am J Chin Med,2011,39(6):1103-1115.
[133] Perry E, Howes MJ. Medicinal plants and dementia therapy:herbal hopes for brain aging?[J].CNS Neurosci Ther,2011,17(6):683-698.
[134]高小青，杜杰，邓莉，等.人参皂甙Rb1对大鼠脑缺血再灌注后巢蛋白表达的影响[J].现代医药卫生,2011,27(2):161-163.
[135]杨进国，夏中元，赵博，等.人参皂甙Rb1在核因子NF-E2相关因子2/血红素氧合酶-1通路减轻肠缺血再灌注致急性肺损伤中的分子机制[J].中华实验外科杂志,2012,29(11):2234-2236.
[136]耿庆，乌达，谢远财，等.人参皂甙Rb1对肺缺血再灌注损伤细胞凋亡及其调控基因表达的影响[J].中国中西医结合急救杂志,2005,12(3):159-161.
[137] Wu Y, Xia ZY, Dou J, Zhang L, et al. Protective effect ofginsenoside Rb1against myocardial ischemia/reperfusion injury instreptozotocin-induced diabetic rats[J].Mol Biol Rep,2011,38(7):4327-4335.
[138]盘强文，冉兵，冯志强，等.人参二醇组皂甙促进受损的培养肾小管细胞增殖的作用及机制研究[J].中国中西医结合急救杂志,2003,10(3):142-145.
[139] Kiefer D, Pantuso T. Panax ginseng[J]. Am Fam Physician.2003,15,68(8):1539-1542.
[140] YANG Shu-long, FENG Zhi-qiang, WU Li-sha. Shenfu injectionprevents kidney from acute ischemia-reperfusion injury inrabbits[J]. Chinese Journal of Pathophysiology,2003,19(3):353-356.
[141]曾庆华，战术，张文杰，等.人参皂甙单体Rb1对豚鼠心肌细胞ICa2+电流阻滞作用的研究[J].白求恩医科大学学报,1997,23(3):265-267.
[142]黄晓光，邵珊，李荣山.人参皂甙Rb1对大鼠急性肾小管损伤的保护作用[J].临床医药实践杂志,2006,15(8):579-581.
[143] Li YK, Chen XC, Zhu YG, et al. Ginsenoside Rb1attenuatesokadaic acid-induced Tau protein hyperphosphorylation in rathippocampal neurons[J]. Sheng Li Xue Bao.2005,57(2):154-160.
[144] Attele AS, Zhou YP, Xie JT, et al. Antidiabetic effects of Panaxginseng berry extract and the identification of an effectivecomponent[J]. Diabetes,2002,51(6):1851-1858.
[145] Yuan QL, Yang CX, Xu P, et al. Neuroprotective effects ofginsenoside Rb1on transient cerebral ischemia in rats[J].Brain Res,2007,1167:1-12.
[146] Ji YC, Kim YB, Park SW, et al. Neuroprotective effect of ginsengtotal saponins in experimental traumatic brain injury[J]. J KoreanMed Sci,2005,20(2):291-296.
[147][147]Yoshikawa T, Akiyoshi Y, Susumu T, et al. Ginsenoside Rb1reduces neurodegeneration in the peri-infarct area of athromboembolic stroke model in non-human primates[J].JPharmacol Sci,2008,107(1):32-40.
[148]李君庆，张香阁，张均田.人参皂甙Rg1抗神经细胞凋亡作用机制的研究[J].药学学报,1997,32(6):406-410.
[149]朱陵群，范吉平，黄放福.人参皂甙Rb1对大鼠胎鼠海马神经细胞凋亡的影响[J].中国病理生理杂志.2001,17(12):1229-1231.
[150]聂荣庆，李扣华，胡国柱等.人参皂甙Rb1抗新生大鼠大脑皮层神经细胞缺氧性凋亡研究[J].中国康复理论与实践.2004,10(12):723-725.
[151]陈晓春，朱元贵，王小众，等.人参皂甙Rg1对PC12细胞凋亡保护作用的可能机制[J].药学学报,2001,36(6):411-414.
[152] Cosulich S C, Worrall V, Hedge PJ, et al. Regulation of apoptosisby BH3domains in a cell-free system[J]. Curr Biol,1997,7:913-920.
[153]郭若霖，万晓华，陈晓建.人参皂甙Rg1和Rb1对脐血CD34＋细胞凋亡的影响[J].华现代临床医学杂志,2004,2(4):385-387.
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