黄芪对低氧环境下血管内皮细胞生长因子/基质细胞衍生因子-1诱导人骨髓间充质干细胞分化、迁移的干预作用的研究
摘要
目的
自体骨髓干细胞移植是将外周血或骨髓中的干细胞移植到缺血的肢体肌肉或闭塞的血管中,使其分化、形成新生毛细血管,改善甚至恢复下肢血流以达到治疗下肢缺血的目的。如何在下肢缺血缺氧的环境中,提高干细胞向VECs分化和迁移能力,成为研究的重点。目前以黄芪为代表的益气活血中药在中西医结合治疗下肢PAOD方面,发挥了重要作用。本研究模拟人体内低氧环境,研究黄芪和VEGF、SDF-1重要细胞因子对hBMSCs向VECs分化及迁移能力的影响,探讨中药干预的主要靶点、作用时机等关键因素,为临床运用提供科学依据。
方法
1黄芪对低氧环境下VEGF诱导hBMSCs分化的干预作用的研究
随机将hBMSCs分为七组,分别为VEGF+常氧组、黄芪+常氧组、VEGF+黄芪+常氧组、低氧对照组、VEGF+低氧组、黄芪+低氧组、VEGF+黄芪+低氧组。将常氧三组置于普通C02细胞培养箱(21%02)中；低氧四组置于三气培养箱(5%O2)中培养。培养7天后,免疫细胞化学法检测CD34、CD31、vWF、VEGFR-2. HIF-la标记物。
2 AMI对低氧条件下SDF-1诱导hBMSCs迁移的干预作用的研究
随机分为7组,分别为SDF+常氧组、黄芪+常氧组、SDF+黄芪+常氧组、低氧对照组、SDF+低氧组、黄芪+低氧组、SDF+黄芪+低氧组共七组。将hBMSCs细胞悬液放入Transwell系统的上室,将含不同药物的细胞培养液加入到Transwell系统的下室中。将常氧三组Transwell系统置于普通CO2细胞培养箱(21%02)中；低氧四组Transwell系统置于三气培养箱(5%O2)中培养。培养48h后,取上室,酒精棉球擦掉上室膜上未迁移的细胞,95%酒精固定10min,苏木素染色5min,随机选择3个连续显微镜视野(×200)计数迁移到上室膜下的细胞,取平均数。
结果
1黄芪对低氧条件下VEGF诱导hBMSCs分化的干预作用的研究
(1)CD34阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01,p<0.05)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01,p<0.05)；低氧对照组与其他三组相比较,显著降低(p<0.01)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
(2)CD31阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组组与其他三组相比较,显著升高(p<0.01)；低氧对照组组与其他三组相比较,显著降低(p<0.01,p<0.05)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01,p<0.05)
(3)vWF阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01)；低氧对照组组与其他三组相比较,显著降低(p<0.01)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
(4) VEGFR-2阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01)；低氧对照组与其他三组相比较,显著升高(p<0.01)。
3)与VEGF+常氧组相比较,VEGF+低氧组显著升高(p<0.05)；与黄芪+常氧组相比较,黄芪+低氧组显著升高(p<0.01)；VEGF+黄芪+常氧组与VEGF+黄芪+低氧组组间无统计学意义(p>0.05)。
(5)HIF-1α阳性率(%)
1)在常氧培养三组中,各组间无统计学意义(p>0.05)。
2)在低氧培养四组中,各组间无统计学意义(p>0.05)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
2黄芪对低氧条件下SDF-1诱导hBMSCs迁移的干预作用的研究
(1)在常氧培养三组中,SDF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01,p<0.05)。
(2)在低氧培养四组中,SDF+黄芪+低氧组与其他三组相比较,显著升高(p<.01)；与SDF+低氧组相比较,低氧对照组显著升高(p<0.01)；低氧对照组与黄芪+低氧组无统计学意义(p>0.05)。
(3)与SDF+黄芪+常氧组相比较,SDF+黄芪+低氧组组间显著升高(p<0.05)；SDF+常氧组与SDF+低氧组、黄芪+常氧组与黄芪+低氧组组间无统计学意义(p>0.05)。
结论
1低氧环境下黄芪可能对BMSCs向VECs分化有促进作用,可能与对HIF-1α和VEGF的影响有关。
2在常氧和低氧环境中黄芪与SDF-1联合使用可促进BMSCs迁移：而在低氧环境中,单独应用黄芪没有明显的促进作用。
Objective
To improve or even recover blood flow through transplanting BMSCs into the ischemic appendicular muscle or occlusive vessel contributing to the formation of new blood vessels is the purpose of Autologous Bone Marrow Stem Cell Transplantation. The current focus of the study on stem cell is how to improve the migration and differentiation capabilities. TCM drugs based on replenishing qi and activating blood represented by Astragalus have played an important role in treatment of lower extremity PAOD with therapies of Integrated Traditional and Western medicine. We study the effect on the capabilities of migrating to the lesion sites and differentiating into vascular endothelial cells influenced by Astragalus, VEGF and SDF-1 by simulating hypoxic environment of human body, to explore the key factors, such as the main target and timing of the intervention of TCM drugs for providing scientific data for clinical use.
Methods
1 The study on the intervention of Astragalus on the role of VEGF which induced hBMSCs to differentiate into vascular endothelial cells in hypoxic environment
HBMSCs were randomly divided into 7 groups:VEGF+Normoxia group, Astragalus+ Normoxia group, VEGF+Astragalus+Normoxic group, Hypoxic control group, VEGF+Hypoxia group, Astragalus+Hypoxia group, Astragalus+VEGF+Hypoxia group. The three normxic groups were placed in ordinary cell culture incubator (21%O2); The four hypoxic groups in the special cell culture incubator (5%O2). Cultured for 7 days, cells were evaluated with CD34, CD31, vWF, VEGFR-2, HIF-la markers by immunocytochemistry.
2 The study on the intervention of Astragalus on the role of SDF-1 which induced hBMSCs to migrate to the lesion sites in hypoxic environment
HBMSCs were randomly divided into 7 groups:SDF+Normoxia group, Astragalus+ Normoxia group, SDF+Astragalus+Normoxia group, Hypoxic control group, SDF+Hypoxia group, Astragalus+Hypoxia group, SDF+Astragalus+Hypoxia group. hBMSC cell suspensions were placed into the upper chamber of the Transwell system, cell culture medium with different drugs into the lower chamber.The three normxic groups were placed in ordinary cell culture incubator (21% O2); The four hypoxic groups in the special cell culture incubator (5% O2). After cultured for 48h, we removed the upper chamber of the Transwell system, wiped off cells on the membrane of the upper chamber that did not migrate, immersed the membrane with 95% alcohol in 10min, stained cells with hematoxylin in 5min, at last randomly selected three consecutive microscope visual field (×200) to count cells below the membrane, taking the average.
Results
1 The study on the intervention of Astragalus on the role of VEGF which induced hBMSCs to differentiate into vascular endothelial cells in hypoxic environment
(1) the positive rate of CD34 (%)
1) Among the three normoxic groups, the positive rate of CD34 in VEGF+Astragalus+ Normoxia group was significantly higher than that of others (p<0.01, p<0.05).
2) Among the four hypoxic groups, the positive rate of CD34 in VEGF+Astragalus +Hypoxia group was significantly higher than that of others (p<0.01,p＜0.05); The positive rate of CD34 in Hypoxic control group was significantly lower than that of others (p<0.01).
3) The positive rate of CD34 in each hypoxic group was significantly higher than that of the corresponding normoxic group (p<0.01).
(2)The positive rate of CD31(%)
1)Among the three normoxic groups, compared with the other two groups, the positive rate of CD31 in VEGF+Astragalus+normxia group was significantly higher than that of others (p <0.01).
2)Among the four hypoxic groups, the positive rate of CD31 in VEGF+Astragalus+hypoxia group was significantly higher than that of others (p<0.01); The positive rate of CD31 in hypoxic control group was significantly lower than that of others (p<0.01, p<0.05).
3) The positive rate of CD31 in each hypoxic group was significantly higher than that of the corresponding normoxic group (p<0.01,p＜0.05).
(3) The positive rate of vWF (%)
1)Among the three normoxic groups, the positive rate of vWF in VEGF+astragalus+ normoxia group was significantly higher than that of others(p<0.01).
2)Among the four hypoxic groups, the positive rate of vWF in VEGF+astragalus+hypoxia group was significantly higher than that of others(p<0.01); The positive rate of vWF in hypoxic control groups was significantly lower than that of others(p<0.01).
3) Each hypoxia group was significantly higher than that of the corresponding normoxic group (p<0.01).
(4)The positive rate of VEGFR-2(%)
1)Among the three normoxic groups, the positive rate of VEGFR-2 in VEGF+Astragalus+ normoxia group was significantly higher than that of others (p<0.01).
2) Among the hypoxia groups, the positive rate of VEGFR-2 in VEGF+Astragalus+Hypoxia group was significantly higher than that of others(p<0.01); the positive rate of VEGFR-2 in hypoxic control group was significantly higher than that of others(p<0.01).
3)The positive rate of VEGFR-2 in VEGF+Hypoxia group was significantly higher than that ofVEGF+Normoxia group(p<0.05); The positive rate of VEGFR-2 in Astragalus+Hypoxia group was significantly higher than that of Astragalus+Normoxia group (p<0.01); The positive rate of VEGFR-2 in VEGF+Astragalus+Hypoxia group was no significantly highe than that of VEGF+Astragalus+Normoxia group(p>0.05).
(5)The positive rate of HIF-1α(%)
1)Among the three normoxic groups, the positive rate of HIF-1αin each group was not significantly higher than that of others(p>0.05).
2)Among the four hypoxic groups, the positive rate of HIF-1αin each group was not significantly higher than that of others (p>0.05).
3) The positive rate of HIF-1αin each hypoxic group increased significantly than that of the corresponding normoxic groups(p<0.01).
2 The study on the intervention of Astragalus on the role of SDF-1 which induced hBMSCs to migrate to the lesion sites in hypoxic environment
(1)Among the three normoxic groups, the ability of migration of hBMSCs in SDF+Astragalus+Normoxia group was significantly higher than that of others (p<0.01, p<0.05).
(2)Among the four hypoxic groups, the ability of migration of hBMSCs in SDF+Astragalus+hypoxia group was significantly higher than that of others (p<0.01); the ability of migration of hBMSCs in SDF+Hypoxia group was significantly higher than that in hypoxic control group (p＜0.01); the ability of migration of hBMSCs in hypoxia+Astragalus group was not significantly higher than that of Hypoxic control group(p> 0.05).
(3)The ability of migration of hBMSCs in SDF+Astragalus+Hypoxia group was significantly higher than that in SDF+Astragalus+Normoxia group(p<0.05); The ability of migration of hBMSCs in SDF+Normoxia group was not significantly higher than that in SDF+ Hypoxia group (p<0.05); The ability of migration of hBMSCs in Astragalus+Normoxia group was not significantly higher than that in Astragalus+Hypoxia group (p<0.05);
Conclusions
1 Astragalus may promote the ability of differentiating into the VECs of BMSCs in hypoxic environment, which may be related to HIF-1 a and VEGF.
2 In normoxic and hypoxic environment,Astragalus combined with SDF-1 can promote the migration of BMSCs.In the hypoxic environment, only Astragalus can not promote the migration of BMSCs.
自体骨髓干细胞移植是将外周血或骨髓中的干细胞移植到缺血的肢体肌肉或闭塞的血管中,使其分化、形成新生毛细血管,改善甚至恢复下肢血流以达到治疗下肢缺血的目的。如何在下肢缺血缺氧的环境中,提高干细胞向VECs分化和迁移能力,成为研究的重点。目前以黄芪为代表的益气活血中药在中西医结合治疗下肢PAOD方面,发挥了重要作用。本研究模拟人体内低氧环境,研究黄芪和VEGF、SDF-1重要细胞因子对hBMSCs向VECs分化及迁移能力的影响,探讨中药干预的主要靶点、作用时机等关键因素,为临床运用提供科学依据。
方法
1黄芪对低氧环境下VEGF诱导hBMSCs分化的干预作用的研究
随机将hBMSCs分为七组,分别为VEGF+常氧组、黄芪+常氧组、VEGF+黄芪+常氧组、低氧对照组、VEGF+低氧组、黄芪+低氧组、VEGF+黄芪+低氧组。将常氧三组置于普通C02细胞培养箱(21%02)中；低氧四组置于三气培养箱(5%O2)中培养。培养7天后,免疫细胞化学法检测CD34、CD31、vWF、VEGFR-2. HIF-la标记物。
2 AMI对低氧条件下SDF-1诱导hBMSCs迁移的干预作用的研究
随机分为7组,分别为SDF+常氧组、黄芪+常氧组、SDF+黄芪+常氧组、低氧对照组、SDF+低氧组、黄芪+低氧组、SDF+黄芪+低氧组共七组。将hBMSCs细胞悬液放入Transwell系统的上室,将含不同药物的细胞培养液加入到Transwell系统的下室中。将常氧三组Transwell系统置于普通CO2细胞培养箱(21%02)中；低氧四组Transwell系统置于三气培养箱(5%O2)中培养。培养48h后,取上室,酒精棉球擦掉上室膜上未迁移的细胞,95%酒精固定10min,苏木素染色5min,随机选择3个连续显微镜视野(×200)计数迁移到上室膜下的细胞,取平均数。
结果
1黄芪对低氧条件下VEGF诱导hBMSCs分化的干预作用的研究
(1)CD34阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01,p<0.05)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01,p<0.05)；低氧对照组与其他三组相比较,显著降低(p<0.01)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
(2)CD31阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组组与其他三组相比较,显著升高(p<0.01)；低氧对照组组与其他三组相比较,显著降低(p<0.01,p<0.05)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01,p<0.05)
(3)vWF阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01)；低氧对照组组与其他三组相比较,显著降低(p<0.01)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
(4) VEGFR-2阳性率(%)
1)在常氧培养三组中,VEGF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01)。
2)在低氧培养四组中,VEGF+黄芪+低氧组与其他三组相比较,显著升高(p<0.01)；低氧对照组与其他三组相比较,显著升高(p<0.01)。
3)与VEGF+常氧组相比较,VEGF+低氧组显著升高(p<0.05)；与黄芪+常氧组相比较,黄芪+低氧组显著升高(p<0.01)；VEGF+黄芪+常氧组与VEGF+黄芪+低氧组组间无统计学意义(p>0.05)。
(5)HIF-1α阳性率(%)
1)在常氧培养三组中,各组间无统计学意义(p>0.05)。
2)在低氧培养四组中,各组间无统计学意义(p>0.05)。
3)常氧和低氧相对应组间比较,低氧各组显著升高(p<0.01)。
2黄芪对低氧条件下SDF-1诱导hBMSCs迁移的干预作用的研究
(1)在常氧培养三组中,SDF+黄芪+常氧组与其他两组相比较,显著升高(p<0.01,p<0.05)。
(2)在低氧培养四组中,SDF+黄芪+低氧组与其他三组相比较,显著升高(p<.01)；与SDF+低氧组相比较,低氧对照组显著升高(p<0.01)；低氧对照组与黄芪+低氧组无统计学意义(p>0.05)。
(3)与SDF+黄芪+常氧组相比较,SDF+黄芪+低氧组组间显著升高(p<0.05)；SDF+常氧组与SDF+低氧组、黄芪+常氧组与黄芪+低氧组组间无统计学意义(p>0.05)。
结论
1低氧环境下黄芪可能对BMSCs向VECs分化有促进作用,可能与对HIF-1α和VEGF的影响有关。
2在常氧和低氧环境中黄芪与SDF-1联合使用可促进BMSCs迁移：而在低氧环境中,单独应用黄芪没有明显的促进作用。
Objective
To improve or even recover blood flow through transplanting BMSCs into the ischemic appendicular muscle or occlusive vessel contributing to the formation of new blood vessels is the purpose of Autologous Bone Marrow Stem Cell Transplantation. The current focus of the study on stem cell is how to improve the migration and differentiation capabilities. TCM drugs based on replenishing qi and activating blood represented by Astragalus have played an important role in treatment of lower extremity PAOD with therapies of Integrated Traditional and Western medicine. We study the effect on the capabilities of migrating to the lesion sites and differentiating into vascular endothelial cells influenced by Astragalus, VEGF and SDF-1 by simulating hypoxic environment of human body, to explore the key factors, such as the main target and timing of the intervention of TCM drugs for providing scientific data for clinical use.
Methods
1 The study on the intervention of Astragalus on the role of VEGF which induced hBMSCs to differentiate into vascular endothelial cells in hypoxic environment
HBMSCs were randomly divided into 7 groups:VEGF+Normoxia group, Astragalus+ Normoxia group, VEGF+Astragalus+Normoxic group, Hypoxic control group, VEGF+Hypoxia group, Astragalus+Hypoxia group, Astragalus+VEGF+Hypoxia group. The three normxic groups were placed in ordinary cell culture incubator (21%O2); The four hypoxic groups in the special cell culture incubator (5%O2). Cultured for 7 days, cells were evaluated with CD34, CD31, vWF, VEGFR-2, HIF-la markers by immunocytochemistry.
2 The study on the intervention of Astragalus on the role of SDF-1 which induced hBMSCs to migrate to the lesion sites in hypoxic environment
HBMSCs were randomly divided into 7 groups:SDF+Normoxia group, Astragalus+ Normoxia group, SDF+Astragalus+Normoxia group, Hypoxic control group, SDF+Hypoxia group, Astragalus+Hypoxia group, SDF+Astragalus+Hypoxia group. hBMSC cell suspensions were placed into the upper chamber of the Transwell system, cell culture medium with different drugs into the lower chamber.The three normxic groups were placed in ordinary cell culture incubator (21% O2); The four hypoxic groups in the special cell culture incubator (5% O2). After cultured for 48h, we removed the upper chamber of the Transwell system, wiped off cells on the membrane of the upper chamber that did not migrate, immersed the membrane with 95% alcohol in 10min, stained cells with hematoxylin in 5min, at last randomly selected three consecutive microscope visual field (×200) to count cells below the membrane, taking the average.
Results
1 The study on the intervention of Astragalus on the role of VEGF which induced hBMSCs to differentiate into vascular endothelial cells in hypoxic environment
(1) the positive rate of CD34 (%)
1) Among the three normoxic groups, the positive rate of CD34 in VEGF+Astragalus+ Normoxia group was significantly higher than that of others (p<0.01, p<0.05).
2) Among the four hypoxic groups, the positive rate of CD34 in VEGF+Astragalus +Hypoxia group was significantly higher than that of others (p<0.01,p＜0.05); The positive rate of CD34 in Hypoxic control group was significantly lower than that of others (p<0.01).
3) The positive rate of CD34 in each hypoxic group was significantly higher than that of the corresponding normoxic group (p<0.01).
(2)The positive rate of CD31(%)
1)Among the three normoxic groups, compared with the other two groups, the positive rate of CD31 in VEGF+Astragalus+normxia group was significantly higher than that of others (p <0.01).
2)Among the four hypoxic groups, the positive rate of CD31 in VEGF+Astragalus+hypoxia group was significantly higher than that of others (p<0.01); The positive rate of CD31 in hypoxic control group was significantly lower than that of others (p<0.01, p<0.05).
3) The positive rate of CD31 in each hypoxic group was significantly higher than that of the corresponding normoxic group (p<0.01,p＜0.05).
(3) The positive rate of vWF (%)
1)Among the three normoxic groups, the positive rate of vWF in VEGF+astragalus+ normoxia group was significantly higher than that of others(p<0.01).
2)Among the four hypoxic groups, the positive rate of vWF in VEGF+astragalus+hypoxia group was significantly higher than that of others(p<0.01); The positive rate of vWF in hypoxic control groups was significantly lower than that of others(p<0.01).
3) Each hypoxia group was significantly higher than that of the corresponding normoxic group (p<0.01).
(4)The positive rate of VEGFR-2(%)
1)Among the three normoxic groups, the positive rate of VEGFR-2 in VEGF+Astragalus+ normoxia group was significantly higher than that of others (p<0.01).
2) Among the hypoxia groups, the positive rate of VEGFR-2 in VEGF+Astragalus+Hypoxia group was significantly higher than that of others(p<0.01); the positive rate of VEGFR-2 in hypoxic control group was significantly higher than that of others(p<0.01).
3)The positive rate of VEGFR-2 in VEGF+Hypoxia group was significantly higher than that ofVEGF+Normoxia group(p<0.05); The positive rate of VEGFR-2 in Astragalus+Hypoxia group was significantly higher than that of Astragalus+Normoxia group (p<0.01); The positive rate of VEGFR-2 in VEGF+Astragalus+Hypoxia group was no significantly highe than that of VEGF+Astragalus+Normoxia group(p>0.05).
(5)The positive rate of HIF-1α(%)
1)Among the three normoxic groups, the positive rate of HIF-1αin each group was not significantly higher than that of others(p>0.05).
2)Among the four hypoxic groups, the positive rate of HIF-1αin each group was not significantly higher than that of others (p>0.05).
3) The positive rate of HIF-1αin each hypoxic group increased significantly than that of the corresponding normoxic groups(p<0.01).
2 The study on the intervention of Astragalus on the role of SDF-1 which induced hBMSCs to migrate to the lesion sites in hypoxic environment
(1)Among the three normoxic groups, the ability of migration of hBMSCs in SDF+Astragalus+Normoxia group was significantly higher than that of others (p<0.01, p<0.05).
(2)Among the four hypoxic groups, the ability of migration of hBMSCs in SDF+Astragalus+hypoxia group was significantly higher than that of others (p<0.01); the ability of migration of hBMSCs in SDF+Hypoxia group was significantly higher than that in hypoxic control group (p＜0.01); the ability of migration of hBMSCs in hypoxia+Astragalus group was not significantly higher than that of Hypoxic control group(p> 0.05).
(3)The ability of migration of hBMSCs in SDF+Astragalus+Hypoxia group was significantly higher than that in SDF+Astragalus+Normoxia group(p<0.05); The ability of migration of hBMSCs in SDF+Normoxia group was not significantly higher than that in SDF+ Hypoxia group (p<0.05); The ability of migration of hBMSCs in Astragalus+Normoxia group was not significantly higher than that in Astragalus+Hypoxia group (p<0.05);
Conclusions
1 Astragalus may promote the ability of differentiating into the VECs of BMSCs in hypoxic environment, which may be related to HIF-1 a and VEGF.
2 In normoxic and hypoxic environment,Astragalus combined with SDF-1 can promote the migration of BMSCs.In the hypoxic environment, only Astragalus can not promote the migration of BMSCs.
引文
[1]Acker H. PO2 chemoreception in arterial chemoreceptors[J].Ann Rev Phys,1989,51:835-844.
[2]Goldberg MA,Schneider TJ.Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin[J]. J Biol Chem,1994,269(6): 4355-4359.
[3]Katz BZ, Zamir E, Bershadsky A,et al. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions[J].Mol Bio Cell,2000,11(3):1047-1060.
[4]金惠铭,王建枝,吴立玲,等.缺氧-病理生理学[M].北京：人民卫生出版社,2004：76-87.
[5]Geng YJ.Molecular mechanisms for cardiovascular stem cell apoptosis and growth in the hearts with atherosclerotic coronary disease and isehemic heart failure[J].Ann NY Acad Sci,2006,1010:687-697.
[6]Zhu W,Chen J,Cong X,et al.Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells[J].Stem Cells.2006,24(2):416-425.
[7]Follmar KE,Decroos FC,Prichard HL,et al.Effects of glutamine,glucose,and oxygen concen-tration on the metabolism, and proliferation of rabbit adipose-derived stem cells[J].Tissue Eng,2006,12(12):3525-3533
[8]Mylotte LA,Duffy AM,Murphy M,et al.Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment[J].Stem Cells,2008,26(5):1325-1336.
[9]Greijer AE,Van der Wall E.The role of hypoxia inducible factor 1(HIF-1 in hypoxia induced apoptosis[J] J Clin Pathol,2004,57(10):1009-1014.
[10]Dispersyn GD, Borgers M. Apoptosis in the heart:about programmed cell death and survival[J]. News Physiol Sci,2001,16(1):41-47.
[11]齐国先,孔宏亮,霍鑫,等.缺氧环境下大鼠骨骨髓间充质干细胞凋亡相关蛋自和mRNA的表达[J].中国组织化学与细胞化学杂志,2008,17(2)：140-143.
[12]Jian-an WANQTie-long CHEN,Jun JIANQet al.Hypoxic preconditioning attenuates hypoxia/ reoxygenation-induced apoptosis in mesenchymal stem cells[J].Acta Pharmacologica Sinica.2008, 29(1):74-82.
[13]Tang YL,Tang Y,Zhang YC,et al.Improved graft mesenchymal stem cell survival in isehemic heart with a hypoxia-regulated heme oxygenase-I vector[J].J Am Coll Cardiol,2005,46(7): 1339-1350.
[14]Mangi AA,Noiseux N,Kong D,et al.Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts [J].Nat Med,2003,9(9):1195-1201.
[15]孔宏亮,张利群,齐国先,等.Akt基因转染对骨髓间充质干细胞缺氧凋亡和增殖的影响[J].中国组织化学与细胞化学杂志,2008,17(3)：225-231.
[16]Lord-Dufour S,Copland IB,Levros LC Jr,et al.Evidence for transcriptional regulation of the glucose-6-phosphate transporter by HIF-la:Targeting G6PT with mumbaistatin analogs in hypoxic mesenchymal stromal[J].Stem Cells,2009,27(3):489-497.
[17]Hu X,Yu SP,Fraser JL,et al.Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis[J].J Thoracic Cardiovasc Surg,2008,135(4):799-808.
[18]Brent R.Weil,Troy A. Markel, Jeremy L.Herrmann.Mesenchymal stem cells enhance the viability and proliferation of human fetal intestinal epithelial cells following hypoxic injury via paracrine mechanisms[J].Surgery,2009,146(2):190-197.
[19]D'Ippolito G,Diabim S,Howard GA,et al.Low oxygen tension inhibits Osteogenic differen-tiation and enhances sternness of human MIAMI cells[J].Bone,2006,39(3):513-522.
[20]Rochefort GY,Delorme B,Lopez A,et al.Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia[J].Stem Cells,2006,24(10):2202-2208.
[21]Covello KL, Kehler J, Yu H, et al.HIF-2 regulates Oct-4:effects of hypoxia on stem cell function, embryonic development,and tumor growth[J].Genes Dev,2006(5),20:557-570.
[22]Grayson WL,Zhao F, Izadpanah R,et al.Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs[J]J Cell Physiol,2006,207(2):331-339.
[23]Bosch P, Pratt SL,Stice SL.Isolation,characterization,gene modification.And nuclear repro-gramming of porcine mesenchymal stem cells[J].Biol Reprod,2006,74(1):46-57.
[24]Lin Q,Lee YJ,Yun Z.Differentiation arrest by hypoxia[J].J Biol Chem,2006,281(41):30678-30683.
[25]D'Ippolito QDiabim S,Howard GA,etal.Low oxygen tension inhibits Osteogenic differentiation and enhances sternness of human MIAMI cells[J].Bone,2006,39(3):513-522.
[26]Lennon DP,Edmison JM,Caplan AI.Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension:effects on in vitro and in vivo osteochondrogenesis[J].J Cell Physiol, 2001,187(3):345-355.
[27]Xie XJ,Wang JA,Cao J,Zhang X.Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions[J].Acta Pharmacol Sin,2006,27(9): 1153-1158.
[28]Moussavi-Harami F,Duwayri Y,Martin JA,et al.Oxygen effects on senescence in chondrocytes and mesenchymal stem cells:consequences for tissue engineering[J].Iowa Orthop J,2004,24:15-20.
[29]Droge W.Free radicals in physiologicall control of cell function[J].Physiol Rev,2002,82(1):47-95.
[30]朱斌,顾春虎,宿学家,等.低氧对大鼠骨髓间质干细胞的影响[J].中国现代医生,2009,47(2)：34-36.
[31]须珏华,周燕,谭文松.低氧促进兔骨髓间充质干细胞增殖[J].基础医学与临床,2008,28(12)：1239-1242.
[32]李海生,陈金武,朱玲玲,等.持续低氧增强人骨髓间充质干细胞体外增殖[J].基础医学与临床,2005,25(3)：268-271.
[33]Yonghui Jin, Tomohisa Kato, Moritoshi Furu,et al. Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase[J].Biochemical and Biophysical Research Communications,2010,391(3):1471-1476.
[34]Genbacev O, M.C.Simon,R. Johnson.:The biology of hypoxia:the role of oxygen sensing in development,normal function,and disease[J].Genes Dev,2004,18(18):2183-2194.
[35]Genbacev,O,Y Zhou,J.W:Ludlow,et al.Regulation of human placental development by oxygen tension[J].Science1997,277(5332):1669-1672.
[36]Schipani,E.,H.E.Ryan,S.Didrickson,et al.Hypoxia in cartilage:HIF-1 is essential for chondrocyte growth arrest and survival[J].Genes Dev,2001,15(21):2865-2876.
[37]Studer L,Csete M,Lee SH,et al.Enhanced proliferation,survival,and dopaminergic differenti-ation of CNS precursors in lowered oxygen[J].J Neurosei,2000,20(19):7371-7383.
[38]Yun Z.,H.L.Maecker,R.S.Johnson,et al.Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stral3:a mechanism for regulation of adipogenesis by hypoxia[J].Dev Cell,2002,2(3):331-341.
[39]Silver IA. Measurement of pH and ionic composition of pericellular sites[J].Philos Trans R Soc Lond B Biol Sci,1975,271(912):261-272.
[40]Wang DW; Fermor B,Gimble JM,et al.Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells[J].J Cell Physiol.2005,204(1):184-91.
[41]Kanichai M, Ferguson D, Prendergast PJ,et al. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells:a role for AKT and hypoxia-inducible factor (HIF)-l alpha[J]. J Cell Physiol,2008,216(3):708-715
[42]Wasim S. Khan, Adetola B. Adesida, Simon R. Tew,et al.Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions[J].Journal of Orthopaedic Research,2010,28(6):834-840.
[43]MalladiP,Xu Y,Chiou M,Giaccia AJ,et al.Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells[J].Am J Cell Physiol,2006,290(4):1139-1146.
[44]Kanichai M,Ferguson D,Prendergast PJ,et al.Hypoxia promotes chondrogenesis in rat mesen-chymal stem cells:a role for AKT and hypoxia-inducible factor (HIF)-la[J].J Cell Physiol, 2008,216(3):708-715.
[45]Martin-Rendon E,Hale SJ,Ryan D,et al.Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia[J].Stem Cells,2007,25(4): 1003-1012.
[46]Tondevold E, Eriksen J, Jansen E. Observation on long bone medullary pressures in relation to arterial PO2, PCO2, and pH in the anesthetized dog[J]. Acta Orthop Scand,1979,50:645.
[47]Grant JL,Smith B. Bone marrow gas tensions, bone marrow blood flow and erythropoiesis in man[J].Ann Int Med,1963,58:801-809.
[48]Kofoed H, Sjontoft E, Siemssen SO,et al. Bone marrow circulationafter osteotomy:Blood flow PO2, CO2, and pressure studied in dogs[J]. Acta Orthop Scand,1985,56(5):400-403.
[49]Maniatopoulos C,Sodek J,Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats[J]. Cell Tissue Res,1988,254 (2):317-330.
[50]Volkmer E, Kallukalam BC, Maertz J, et al.Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation[J].Tissue Eng Part A,2010,16(1):153-164.
[51]Lee JH,Kemp DM.Human adipose-derived stem cells display myogenic potential and perturbed function in hypoxic conditions[J].Biochem Biophys Res Commun,2006,341(3):882-888.
[52]Ali Salim, Randall P. Nacamuli, Elise F. Morgan,et al. Transient Changes in Oxygen Tension Inhibit Osteogenic Differentiation and Runx2 Expression in Osteoblasts[J].The Journal of Biological Chemistry,2004,279(38):40007-40016.
[53]Potier E, Ferreira E, Andriamanalijaona R,et al. Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression[J]. Bone,2007,40(4):1078-1087.
[54]Fink T, Abildtrup L,Fogd K,et al.Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia[J].Stem Cells,2004,22(7):1346-1355.
[55]Hongying Ren,Ying Cao,Qinjun Zhao,et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions [J]. Biochemical and Biophysical Research Communications, 2006,347(1):12-21.
[56]Utting JC.Robins SP,Brandao-Burch A,et al.Hypoxia inhibits the growth,differantiation and bone forming capacity of rat osteoblasts[J].Experimental Cell Research[J].2006,312(10):1693-1702.
[57]Zhou S,Lechpammer S,Greenberger JS,et al. Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling[J].J Biol Chem,2005,280(24):22688-22696.
[58]Kopen GC,Prokop DJ,Phinney DQet al. Marrow stromal cells migrate through out for brain and cerebellum,and they differentiate into astrocytes after injection into neonatal mouse brain[J]. Proc Natl Acad Sci USA,1999,96(19):10711-10716.
[59]Esneault E,Pacary E,Eddi D,et al. Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab,2008,28(9):1552-1563.
[60]Pacary E, Legros H,Bernaudin M,et al. Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells[J]. J Cell Sci.2006,119(13):2667-2678.
[61]Annabi B, Lee Y, Turcotte S.et al.Hypoxia promotes murine bone marrow-derived stromal cell migration and tube formation[J].Stem Cells,2003,21(3):337-347.
[62]Kaiming Liu,Luxiang Chi,Liang Guo,et al. The interactions between brain microvascular endothelial cells and mesenchymal stem cells under hypoxic conditions[J].Microvascular Research,2008,75(1):59-67.
[63]Rosova I,Dao M,Capoccia B,et al.Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells[J].Stem Cells,2008,26(8): 2173-2182.
[64]Xiao-jie XIE, Jian-an WANG, Jiang CAO,et al.Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions[J].Acta Pharmacologica Sinica,2006,27(9):1153-1158.
[65]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J].J Biol Chem,2006,281(22):15554-15563.
[66]Radini DJ.Gurtner GC.Homing to hypoxia:HIF-1 as a mediator of progenitor cell recruitment to injured tissue[J]. Trends Cardiovasc Med,2005,15(2):57-63.
[67]Zhu H,Mitsuhashi N,Klein A,et al.The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix[J].Stem Cells,2006,24(4):928-935.
[68]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1 [J].J Biol Chem,2006, 281(22):15554-15563.
[69]Bhakta S,Hong E,Koc O.The Surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell derived factor-1 in vitro but does not decrease apoptosis under Serum deprivation[J]. Cardiovasc Revasc Med,2006,7(1):19-24.
[70]Sun-Young Ju, Kyung-Ah Cho, Su Jin Cho,et al.Effect of hypoxic treatment on bone marrow cells that are able to migrate to the injured liver[J].Cell Biology International,2009,33(1):31-35.
[71]王心蕊,何旭,王医术,等.低氧促进人骨髓间充质干细胞迁移的实验研究[J].中国免疫学杂志,2006,22(12)：1100-1102.
[72]朱洁,周竹娟,龚自力,等.低氧对人骨髓间充质干细胞趋化因子受体CXCR4和CX3CR1表达的影响[J].中国组织工程研究与临床康复,2009,13(23)：4485-4489.
[73]Stellos K, Langer H, Daub K,et al. Platelet-Derived Stromal Cell Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells[J].Circulation,2008,117(2):206-215.
[74]Ramirez-Bergeron DL, Simon MC.Hypoxia-inducible factor and the development of stem cells of the cardiovascular system[J]. Stem Cells,2001,19(4):279-286.
[75]Csete M.Oxygen in the cultivation of stem cells[J].Ann N Y Acad Sci,2005,1049:1-8.
[76]Harris AL.Hypoxia-a key regulatory factor in tumour growth[J].Nat Rev Cancer,2002,2(1):38-47.
[77]Esteban MA,Tran MQHarten SK,et al.Regulation of E-cadherin expression by VHL and hypoxia-inducible factor [J]. Cancer Res,2006,66(7):3567-3575.
[1]耿长山.黄芪的免疫药理作用研究[J].中西医结合杂志,1986,3(1)：62
[2]耿长山,等.黄芪多糖对去T细胞小鼠促进抗体产生机理探讨[J].中国药理通讯,1985,2(2)：14.
[3]陈丽娟.黄芪多糖对小鼠吞噬能力的影响[J].中国药理学报,1981,2(3)：20.
[4]翁玲,刘彦,刘学英,等.黄芪多糖粉针剂对小鼠脾细胞分泌细胞因子及NK杀伤能力的影响[J].中医药学刊,2003,21(9)：1522-1524.
[5]钟国赣,孙晓霞,李云义,等.黄芪皂甙对离体工作心脏的强心作用[J].白求恩医科大学学报,1994,20(5)：448.
[6]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1)：38.
[7]梁明,韩竹梅,梁小光,等.黄芪冻干粉对大鼠离体心脏的作用[J].中草药,2000,31(11)：846-847.
[8]何蕾,江朝光,.黄芪注射液抗心肌细胞再灌注损伤的作用及机制[J].世界急危重病医学杂志,2006,3(4)：1365-1366.
[9]王曦,孟巍,荆洪英.黄芪注射液治疗冠心病心绞痛的临床疗效观察[J].黑龙江医药科学,2004,27(4)：76-77.
[10]徐西.党参、黄芪对血小板聚集的临床及实验研究[J].中药药理与临床,1985,4(4)：32.
[11]高建,徐先祥,徐先俊,等.黄芪总皂甙抗血栓形成作用实验研究[J].中成药,2002,24(2)：116-118.
[12]侯世荣.黄芪口服液治疗慢性肝炎的疗效观察[J].中草药,2000,31(10)：766.
[13]李智军,魏连波,贺丰,等.黄芪多糖治疗大鼠系膜细胞增生性肾炎的实验研究[J].中国中西医结合肾病杂志,2000,1(4)：206.
[14]张英,李铁兵,孙茂波.参芪合剂抗疲劳作用的基础与临床研究[J].中医药学报,1998,26(4)：35.
[15]李卫平,明亮,张艳,等.黄芪多糖耐缺氧作用的实验研究[J].安徽医科大学学报,1995,30(3)：184.
[16]余勤,罗依,董勤,等.黄芪对间质干细胞分化为神经元样细胞的定向诱导作用[J].中华急诊医学杂志,2004,13(12)：826-829.
[17]王勇,陆长青,王凡.黄芪诱大鼠骨髓间充质干细胞分化为神经样细胞的研究[J].解剖学杂志,2006,14(1)：5-8.
[18]王新生,赵荧,李海峰,等.黄芪诱导大鼠骨髓间充质干细胞的分化特点[J].中国组织工程研究与临床康复,2009,13(19)：3785-3789.
[19]王新生,李海峰,赵荧,等.黄芪诱导大鼠骨髓间充质干细胞分化早期胞内钙调蛋白mRNA的转录水平[J].中国组织工程研究与临床康复,2009,13(23)：4495-4499.
[20]Li ZS, Pham TD, Tam ir H, et al. Enteric dopaninergic neurons:definiation, developmental lineage, and effects of extrinsic denerwation[J]. J Neuro sci,2004,24(6):1330-1339.
[21]董晓先,冷水龙,刘金保.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞的基因表达谱[J].中国临床康复,2006,10(21)：1-3.
[22]Smolich BD, Papkoff J. Regulated expression of Wnt family member during neuroectodermal differentiation of P19 embryonal carcinoma cells overexp ression of Wnt-1 pertubs normal differentiation-specific propertiea[J]. Dev Biol,1994,166(1):300-310.
[23]Nusse R, Varmus HE. Wnt genes[J]. Cell,1992;69(7):1073-1087.
[24]Parr BA, Shea MJ, Vassileva G, et al. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds[J]. Development,1993,119(1):247-261.
[25]Hamada-Kanazawa M, Ishikawa K, Nomo to K. Sox 6 overexpression causes cellular aggregation and the neuronal differentiation of P19 embryonic carcinoma cells in the absence of retinoic acid[J]. FEBS Lett,2004:560 (13):192-198.
[26]杨新文,王勇.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞[J].中国组织工程研究与临床康复,2008,12(25)：4996-5000.
[27]王新生,崔慧先,刘华,等.黄芪诱导骨髓间充质干细胞分化进程中细胞内钙离子浓度的动态变化[J].中国组织工程研究与临床康复,2007,11(42)：8469-8472.
[28]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2007,24(1)：37-40.
[29]杨庆有,冼绍祥,孙慧茹,等.黄芪含药血清诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].辽宁中医杂志,2008,35(6)：832-834.
[30]杨博华,朱陵群,张娟子,等.黄芪、三七促进骨髓干细胞体外转化并扩增血管内皮前体细胞(EPC)作用的研究[J].中国中药杂志,2005,30(22)：1761-1763.
[31]邹萍,胡翔,刘德伍.黄芪诱导人骨髓间充质干细胞向表皮样细胞的分化[J].中国组织工程研究与临床康复[J],2009,13(36)：7099-7102.
[32]许春姣,郭峰,高清平,等.骨髓基质干细胞与黄芪-壳聚糖／聚乳酸支架对犬牙周骨缺损再生的影响[J].中南大学学报(医学版),2006,31(4)：512-517.
[33]杨云华,于小华,李双杰,等.黄芪注射液对多柔比星诱导的脐血间充质干细胞凋亡的影响[J].实用儿科临床杂志.2009,24(11)：851-854.
[34]石田寅夫,王秀云,柴丽娟,等.体外培养胚胎神经干细胞的增殖及中药有效成分对其增殖能力的影响[J].天津中医药,2009,26(2)：155-159.
[35]刘建军,姚忠祥,秦茂林,等.单昧黄芪红花丹参注射液对神经干细胞分化影响的初步研究[J].第三军医大学学报,2006,28(14)：1470-1472.
[36]刘静,罗雪,钟善传,等.黄芪皂甙诱导小鼠神经干细胞向神经元分化.第四军医大学学报[J],2009,30(7)：580-583.
[37]张艳军,范祥,胡利民,等.不同治则中药单体对体外培养神经干细胞分化的影响[J].天津中医药,2004,21(2)：156-157.
[38]Gaugler MH,Squiban C,Claraz M,et al. Characterization of the response of human bone marrow endothelial cells to in vitro irradiation[J].Bri J Haemat,1998,103(4):980-989.
[39]刘晓,武正炎,范萍.黄芪在外周血造血干细胞移植中应用的初步实验研究[J].镇江医学院学报,2001,11(1)：15-17.
[40]许勇,杨代耘,钟亚琴,等.复方黄芪注射液对小鼠多能造血干细胞(CFU-S)影响的实验研究[J].四川省卫生管理干部学院学报,1995,14(1)：1-2
[41]Fennie C, Cheng J, Dowbenko D,et al.CD34+endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors [J]. Blood,1995,86(12):4454-4467.
[42]Sansilvestri P, Cardoso AA,Batard P, et al. Early CD34 high cells can be separated into KIT high cells in which transforming growth factor-beta[TGF-beta] down modulates c-kit and KIT low cells in which anti-TGF-beta up modulates c-kit[J].Blood,1995,86(5):1729-1735.
[43]Huang E, Nocka K, Beier DR,et al.The Hematopoietic Growth factor KL is encoded by the S/locus and is the ligand of the c-kit receptor,the gene product of the W locus[J].Cell,1990,63(1):225-233.
[44]Zsebo KM,Wypych J,McNiece IK, et al.Identification,purification,and biological characteriza-tion of hematopoietic stem cell factor from buffalo rat live-conditioned medium[J].Cell,1990, 63(1):195-201.
[45]Nishi N,Ishikawa R,Inoue H, et al. Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line[J].Exp Hematol,1996,24(11):1312-1321.
[46]李玛琳,Cardoso AA,Hatzfeld A,等.SCF和TGF-β反义寡核苷酸对CD34+造血细胞的协同作用[J].实验血液学杂志,1996,4(3)：252-256.
[47]祝晓玲,祝彼得.黄芪体外作用对贫血小鼠骨髓基质细胞分泌SCF的影响[J].细胞与分子免疫学杂志,2002,18(4)：396-398.
[48]刘德伍,胡翔,刘德明.黄芪诱导表皮干细胞增殖构建组织工程皮肤治疗皮肤缺损[J].中药药理与临床,2004,20(5)：16-18.
[49]胡翔,邹萍,刘莉玲,等.黄芪对人皮肤表皮干细胞增殖活性的影响[J]中国组织工程研究与临床康复,2009,13(19)：3689-3692.
[50]王蕾,张科伟,赵大伟,等.MTT法检测黄芪和丹参对人乳腺干细胞体外增殖的影响[J].中国组织工程研究与临床康复,2008,12(8)：1418-1421.
[1]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endotheial cells for angiogensis[J].Science,1997,27(5):964-967.
[2]赵春华.干细胞原理、技术与临床.北京：化学工业出版社,2006：3-14；173-174.
[3]Asahara T,Murohara T,Takahashi T,et al.Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].Circ Res,1999;85(3):221-228.
[4]Bussolino F,Mantovani A,Persico G.Molecular mechanism of blood vessel formation[J].Trends Biochem Sci,1997,22(7):251-256.
[5]Yamamoto K,Knodo T,Suzuki S,et al.Molecular evaluation of endothelial progenitor cells in Patiens with ischemic limbs:therapeutic effects by stem Cell trans-plantation[J].Arterisclser Thromb Vasc Bilo,.2004,24(12):192-196.
[6]Pugh CW,Ratccliffe PJ.Regulation of angiogenesis by hypoxia:role of the HIF system[J].Nat Med,2003,9(6):677-684.
[7]Carmeliet P.Angiogenesis in health and disease[J].Nat Med,2003,9(6):653-660.
[8]Li W W,Talcott K E,Zhai A W,et al.The Role of Therapeutic Angiogenesis in Tissue Repair and Regeneration[J].Adv Skin Wound Care,2005,18(9):491-500.
[9]Mazure NM,Brahimi-Horn MC,Pouyssegur J.Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis[J].Curr Pharm Des,2003,9(7):531-541.
[10]Gale NW,Yancopoubs GD.Growth factors acting via endothelial cell specific receptor tyrosine kinases:VEGF's,angiopoietins,and ephrins in vascular development[J].Genes Dev,1999,13(78): 1055-1066.
[11]Thurston G, Rudge JS,Ioffe E,et al.Angiopoietin-1 protects the adult vasculature against plasma leakage[J]. Nat Med,2000,6(36):460-463.
[12]Hirschi K, Rohovsky S,D'Amore P.PDGF,TGF-b and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate[J].J Cell Biol,1998,141(3):805-814.
[13]Fromherz P,Schaden H,Vetter T.Guided outgrowth of leech neurons in culture[J].Neurosci Lett, 1991,129(1):77-80.
[14]Horbert CB,Mclernon TL,Hypolite CL,et al.Micropatterning gradlents and controlling surface densities of photoactivatable biomolecules on self-assembled monolayers of oligo(ethylene glycol)alkanethiolates[J].Chem Biol,1997,4(10):731-773.
[15]杨博华,秦建辉,朱陵群,等,自体骨髓干细胞移植与中药合用治疗下肢缺血性病变[J].北京中医药大学学报,2004,27(6)：76-78.
[16]杨博华,秦建辉,朱陵群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683-684.
[17]杨博华,张娟子,朱陵群,等.黄芪、三七对下肢缺血患者骨髓干细胞体外分化作用的影响[J].中医杂志,2007,48(11)：994-995.
[1]Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell:entity or function? [J].Cell,2001,105(7):829-841.
[2]Traycoff CM, Abboud MR, Laver J,et al. Evaluation of the in vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells[J].Exp Hematol,1994,22 (2):215-222.
[3]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science,1999,284(5411):143-147.
[4]Wakitani S, Saito T, Caplan Al.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J].Muscle nerve,1995,18(12):1417-1426.
[5]Reyes M,Lund T,Lenvik T,et al.Purifccation and ex vivo expansion of postnatal human marrow nesodermal progenitor cell[J].Blood,2001,98(9):2615-2625.
[6]Sanchez Ronos J.Song S,Cardozo Pelaez F,et al.Adult bone marrow strorml cells differentiate into neural cells in vitro[J].Exp Neurol,2000,164(2):247-256.
[7]赵春华.干细胞原理、技术与临床.北京：化学工业出版社,2006：3-14；173-174.
[8]Schattmnan GC,Dunnwald M,Jiao CHH. Biology of bone marrow-derived endothelial cell precursors[J].Am J Physiol Heart Circ Physiol,2007,292(1):1-18.
[9]Krause DS,Theise ND,Collector MI,et al.Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cells. Cell,2001,105(3):369-377.
[10]Kotton DN, Ma BY, Cardoso WV, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium[J]. Development,2001,128(24):5181-5188.
[11]Satoshi Gojo,Noriko Gojo, Yukiji Takeda,et al.In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells[J]. Experimental cell research,2003,288(1):51-59.
[12]Liu, J.W. et al. Characterization of endothelial-like cells derived from human mesenchymal stem cells[J]. J.Thromb.Haemost,2007,5(4):826-834.
[13]Soonpaa,M.H.,et al,Formation of nascent intercalated disks between grafted fetal cardiomyo-cytes and host myocardium[J]. Science,1994.264(5155):98-101.
[14]Ferrara N,Davis-Smyth T. The biology of vascular endothelial growth factor[J]. Endocr,1997, 18(1):4-25.
[15]Benjamin LE,Golijanin D,Itin A,et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor with drawal[J].Clin Invest,1999,103(2):159-165.
[16]Oswald, J., Boxberger, S.,Jorgensen,B.,et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro[J]. Stem Cell,2004,22(3):377-384.
[17]Gang Zhang,Jianye Zhoub, Quanxin Fana, et al.Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation[J]. FEBS Letters,2008,582(19):2957-2964.
[18]Klopper T,et al.High efficient adenoviral-mediated VEGF and Ang-1 gene delivery into osteogenically differentiated human mesenchymal stem cells[J].Microvasc Res,2008,75(l):83-90.
[19]Reyes M,Dudek A, Jahagirdar B, et al. Origin of endothelial progenitors in human postnatal bone marrow[J]. J Clin Invest,2002,109(3):337-346.
[20]Annabi B, Lee Y, Turcotte S.et al.Hypoxia promotes murine bone marrow-derived stromal cell migration and tube formation[J].Stem Cells,2003,21(3):337-347.
[21]Kaiming Liu,Luxiang Chi,Liang Guo,et al. The interactions between brain microvascular endothelial cells and mesenchymal stem cells under hypoxic conditions[J].Microvascular Research,2008,75(1):59-67.
[22]Ivana Rosova, Mo Dao, Ben Capoccia,et al.Hypoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells[J].Stem Cells,2008,26(8):2173-2182.
[23]Ke QD, Costa M Hypoxia Inducible Factor-1(HIF-1) [J].Mol Pharmacol, 2006,70(5):1469-1480.
[24]Semenza CL.O2-regulated gene expression:transcriptional control of cardiorespiratory physiolog by HIF-1[J].J Appl Physiol,2004,96(3):1173-1177.
[25]Lee J W,Bae SH, Jeong J W,et al.Hypoxia inducible factor alpha(HIF-1):its protein stability and biological functions[J].Exp Mol Med,2004.36(1):1-12.
[26]Wang GL,Semenza GL. Characterization of DNA clincling activity by hypoxia of hypoxia inducible factor-1 and regulationgof DNA clincling activity by hypoxia[J].Biol Chem,1993,268 (29):21513-21518.
[27]Brat DJ,Castellano-Sanchez AA.,Hunter SB,et al.Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population[J]. Cancer Res,2004,64(3):920-927.
[28]Semenza CxL. Hypoxia-inducible factor 1:oxygen homeostasis and disease pathophysiology[J]. Trends Mol Med,2001,7(8):345-350.
[29]Brat, D.J., Mapstone, T.B. Malignant glioma physiology:cellular response to hypoxia and its role in tumor progression[J]. Ann Intern Med,2003,138(8):659-668.
[30]Li J,Sh worak N.W,Simons M.Increased reponsiveness of hypoxic endothelial cell to FGF2 is mediated by HIF-lalpha-dependent r egulation of enzymes involved in synthesis of heparin sulfate FGF2-binding sites[J].Cell Sci,2002,115(9):195.
[31]Sun YJ, Jin k,Xie L.VEGF-induced neuroprotection,neurogenesis,and Angiogengsis after focal cerebral ischema[J].J Clin invest,2003,111(12):1843-1851.
[32]Chavez JC,Agani F,Pichiule P.Expression of hypoxic inducible factor-1 in the brain of rats during chronic hypoxia[J].J Appl Physiol,2000,89(5):1937-1942.
[33]Dai Y,Xu M,Wang Y, et al.HIF-lalpha induced-VEGF over expression in bone marrow stem cells protects cardiomyocytes againstischemia[J].J Mol Cell Cardiol,2007,42(6):1036-1044.
[34]D' Ippolito QDiabira S,Howard GA,et al.Low oxygen tension inhibits osteogenic differenti-ation and enhances sternness of human MIAMI cells[J].Bone,2006;39(3):513-522.
[35]Volkmer E, Kallukalam BC, Maertz J, et al.Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation[J].Tissue Eng Part A,2010,16(1):153-164.
[36]熊迎春,洪小平,陈泽斌,等.黄芪对实验性糖尿病大鼠血管内皮细胞形态的影响[J].中医药学刊,2004,22(10),1859.
[37]谢席胜,黄宗文,李秀钧,等.黄芪对高葡萄糖、游离脂肪酸培养的人血管内皮细胞一氧化氮含量的影响[J].中国临床康复,2004,8(30)：6683.
[38]李绚,阎蓉华,罗照田,等.黄芪注射液对人脐静脉血管内皮细胞的增殖作用[J].华西药学杂志,2005,20(1)：48.
[39]雷燕,高倩,李悦山,等.黄芪、当归及其组方促血管内皮细胞增殖作用的研究[J].中国中西医结合杂志,2003,23(10)：753.
[40]哈敏文,李振,何安光.黄芪合剂防止化疗性骨髓抑制的实验研究[J].中国医科大学学报1997；26(5)：449-452.
[41]阙华发,朱元颖,王云飞,等.益气化瘀中药对糖尿病皮肤溃疡大鼠缺氧诱导因子-1α和血管内皮细胞生长因子的影响[J].中西医结合学报,2007,5(2)：165-169.
[42]余勤,罗依,董勤,等.黄芪对间质干细胞分化为神经元样细胞的定向诱导作用[J].中华急诊医学杂志,2004,13(12)：826-829.
[43]王新生,赵荧,李海峰,等.黄芪诱导大鼠骨髓间充质干细胞的分化特点[J].中国组织工程研究与临床康复,2009,13(19)：3785-3789.
[44]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2007,24(1)：37-40.
[45]邹萍,胡翔,刘德伍.黄芪诱导人骨髓间充质干细胞向表皮样细胞的分化[J].中国组织工程研究与临床康复[J],2009,13(36)：7099-7102.
[46]杨博华,秦建辉,朱陵群等,自体骨髓干细胞移植与中药合用治疗下肢缺血性病变[J].《北京中医药大学学报》,2004,27(6)：76-78.
[47]杨博华,秦建辉,朱陵群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683-684.
[48]杨博华,张娟子,朱陵群,等.黄芪、三七对下肢缺血患者骨髓干细胞体外分化作用的影响[J].中医杂志,2007,48(11)：994-995.
[1]Kucia M,RatajcZak J,Reca R,et al.Tissue-specific muscle,neural and liver stem/progenitor cells reside in the bone marrow,respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury [J].Blood cells Mol Dis,2004,32(1):52-57.
[2]Mastsen FA,et al. The relationship of transcutaneous PO2 and laser-Doppler measurement in a human model of local arterial insufficiency[J].Surg Gynecol Obstet 1984,159(5):418-422.
[3]De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells[J]. Blood.2004,104(12):3472-3482.
[4]Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture[J].Leukemia,2003,17(1):160-170.
[5]Ruster B, Gottig S, Ludwig RJ, et al. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells[J].Blood,2006,108(12):3938-3944.
[6]Shih YR, Chen CN,Tsai SW, et al.Growth of mesenchymal stem cells on electrospun type I collagen nanofibers[J].Stem Cells,2006,24(11):2391-2397.
[7]Phinney DQ Baddoo M, Dutreil M, et al. Murine mesenchymal stern cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration[J]. Stem Cells Dev,2006,15(3):437-447.
[8]Hur J,Yoon CH,Lee CS,et al.Akt is a key modular of endothelial progenitor cell trafficking in ischemic muscle[J].Stern Cells,2007,25 (7):1769-1778.
[9]Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+cell on vascular endothelium under shear flow. J Clin Invest,1999,104(9):1199-1211.
[10]Peled A, Petit I, Kollet O,et al.Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4[J].Science,1999; 283(5403):845-848.
[11]Mohle R,Bautz F, Rafii S. et al.The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor 1 [J]. Blood,1998,91(12):4523-4530.
[13]Hiasa K, Ishibashi M, Ohtani K, et al.Gene transfer of stromal cell-derived factor-I alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/ endothelial nitric oxide synthase-related pathway:next-generatian chemokine therapy for therapeutic neovasculorization[J]. Circulation,2004,109(20):2454-2461.
[13]Yamaguchi J, Kusano KF, Masuo O,et al.Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularizatian[J].Circulation. 2003,107(9):1322-1328.
[14]Aiuti A, Webb U, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood[J].J Bxp Med.1997,185(1):111-120.
[15]Togel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms[J].Am J Physiol Renal Physiol, 2005,289(1):31-42.
[16]Ponte AL,Marais E,Gallay N,et al.The in vitro migration capacity of human bone marrow mesenchymal stem cells:comparison of chemokine and growth factor chemotactic activities [J]. Stem Cells,2007,25(7):1737-1745.
[17]Shi M,Li J,Liao L,et al.Regulation of CXCR4 expression in human mesenchymal stem cells by cytolcine treatment:role in homing efficiency in NOD/SCID mice [J]. Haematologica,2007,92(7): 897-904.
[18]Askari AT, Unzek S, Popvic ZB, et al. Effect of stromal cell-derived factor-1 on stem cell homing and tissue regeneration in ischemic cardiomyopathy[J].Lancet,2003,362(9385):697-703.
[19]Ceradini D, Kalkarni A, Callaghan M, et al.Progenitor cell tracking is regulated by hypoxic gradients through HIF-1 induction of SDF-1 [J]. Nat Med,2004,10(8):858-864.
[20]De Falco E, PorceV P, Torella AR, et al, SDF-1 involvement in endothelial phenotype and ischemio-induced recruitment of bone marrow progenitor cells[J].Blood,2004;104(12):3472-3482.
[21]Le Y, Honczarenko M,Glodek AM, et al. CXC chemokine ligand 12-induced focal adhesion kinase activation and segregation into membrane domains is modulated by regulator of G protein signaling 1 in pro-B cells [J].J Immunol,2005,174(5):2582-2590.
[22]Katayama A, Ogino T, Bandoh N, et al. Expression of CXCR4 and its down-regulation by IFN-gamma in head and neck squamous cell carcinoma [J].Clin Cancer Res,2005,11(8):2937-2946.
[23]Wright LM, Maloney W, Yu X, et al. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts [J].Bone,2005,36(5):840-853.
[24]Abbott JD, Huang Y, Liu D, et al. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J]. Circulation,2004,110(21):3300-3305.
[25]Ye Wang, Yubin Deng, Guang-Qian Zhou.SDF-lalpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model [J].Brain Research,2008,1195:104-112.
[26]Thieme, S.,Ryser, M.F., et al..Stromal cell derived factor-1 alpha directed chemoattraction of transiently CXCR4 overexpressing bone marrow stromal cells into functionalized three-dimensional biomimetic scaffolds.Tissue Eng.2009,15(4):687-696.
[27]Xuezhong He, Junyu Ma, Esmaiel Jabbari-Migration of marrow stromal cells in response to sustained release of stromal-derived factor-la from poly(lactide ethylene oxide fumarate) hydrogels.International Journal of Pharmaceutics,2010,390(2):107-116.
[28]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J].J Biol Chem,2006,281(22):15554-15563.
[29]Radini DJ.Gurtner GC.Homing to hypoxia:HIF-1 as a mediator of progenitor cell recruitment to injured tissue[J].Trends Cardiovasc Med,2005,15(2):57-63.
[30]Zhu H,Mitsuhashi N,Klein A,et al.The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix[J].Stem Ceils,2006,24(4):928-935.
[31]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J]. J Biol Chem,2006,281(22):15554-15563.
[32]Bhakta S,Hong E,Koc O.The Surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell derived factor-1 in vitro but does not decrease apoptosis under Serum deprivation[J]. Cardiovasc Revasc Med,2006,7(l):19-24.
[33]Sun-Young Ju, Kyung-Ah Cho, Su Jin Cho,et al.Effect of hypoxic treatment on bone marrow cells that are able to migrate to the injured liver [J]. Cell Biology International,2009,33(1):31-35.
[34]王心蕊,何旭,王医术,等.低氧促进人骨髓间充质干细胞迁移的实验研究[J].中国免疫学杂志,2006,22(12)：1100-1102.
[35]朱洁,周竹娟,龚自力,等.低氧对人骨髓间充质干细胞趋化因子受体CXCR4和CX3CR1表达的影响[J].中国组织工程研究与临床康复,2009,13(23)：4485-4489.
[36]Stellos K, Langer H, Daub K,et al. Platelet-Derived Stromal Cell Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells.Circulation,2008,117(2):206-215.
[37]欧阳长生,王云开,苏淘,等.丹参及血府逐瘀汤含药血清与兔骨髓间充质干细胞的体外迁移：促进还是抑制?[J].中国组织工程研究与临床康复,2009,13(40)：7847-7851.
[38]郭国庆,沈伟哉,钟世镇.丹参素和丹酚酸对胎鼠脑神经干细胞迁移的诱导[J].中国组织工程研究与临床康复,2007,11(7)：1225-1228.
[39]张芙荣,陈君柱,朱军慧,等.葛根素对外周血内皮祖细胞数量和功能的影响[J].中国中药杂志,2004,29(8)：777-781.
[40]王兴祥,尚云鹏,陈君柱,等.银杏叶提取物对外周血内皮祖细胞数量和功能的影响[J].药学学报,2004,39(8)：656-660.
[41]顾俊,王长谦,范华骅,等.白藜芦醇对外周血内皮祖细胞功能的影响[J].心脏杂志,2006,18(6)：617-621.
[2]Goldberg MA,Schneider TJ.Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin[J]. J Biol Chem,1994,269(6): 4355-4359.
[3]Katz BZ, Zamir E, Bershadsky A,et al. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions[J].Mol Bio Cell,2000,11(3):1047-1060.
[4]金惠铭,王建枝,吴立玲,等.缺氧-病理生理学[M].北京：人民卫生出版社,2004：76-87.
[5]Geng YJ.Molecular mechanisms for cardiovascular stem cell apoptosis and growth in the hearts with atherosclerotic coronary disease and isehemic heart failure[J].Ann NY Acad Sci,2006,1010:687-697.
[6]Zhu W,Chen J,Cong X,et al.Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells[J].Stem Cells.2006,24(2):416-425.
[7]Follmar KE,Decroos FC,Prichard HL,et al.Effects of glutamine,glucose,and oxygen concen-tration on the metabolism, and proliferation of rabbit adipose-derived stem cells[J].Tissue Eng,2006,12(12):3525-3533
[8]Mylotte LA,Duffy AM,Murphy M,et al.Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment[J].Stem Cells,2008,26(5):1325-1336.
[9]Greijer AE,Van der Wall E.The role of hypoxia inducible factor 1(HIF-1 in hypoxia induced apoptosis[J] J Clin Pathol,2004,57(10):1009-1014.
[10]Dispersyn GD, Borgers M. Apoptosis in the heart:about programmed cell death and survival[J]. News Physiol Sci,2001,16(1):41-47.
[11]齐国先,孔宏亮,霍鑫,等.缺氧环境下大鼠骨骨髓间充质干细胞凋亡相关蛋自和mRNA的表达[J].中国组织化学与细胞化学杂志,2008,17(2)：140-143.
[12]Jian-an WANQTie-long CHEN,Jun JIANQet al.Hypoxic preconditioning attenuates hypoxia/ reoxygenation-induced apoptosis in mesenchymal stem cells[J].Acta Pharmacologica Sinica.2008, 29(1):74-82.
[13]Tang YL,Tang Y,Zhang YC,et al.Improved graft mesenchymal stem cell survival in isehemic heart with a hypoxia-regulated heme oxygenase-I vector[J].J Am Coll Cardiol,2005,46(7): 1339-1350.
[14]Mangi AA,Noiseux N,Kong D,et al.Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts [J].Nat Med,2003,9(9):1195-1201.
[15]孔宏亮,张利群,齐国先,等.Akt基因转染对骨髓间充质干细胞缺氧凋亡和增殖的影响[J].中国组织化学与细胞化学杂志,2008,17(3)：225-231.
[16]Lord-Dufour S,Copland IB,Levros LC Jr,et al.Evidence for transcriptional regulation of the glucose-6-phosphate transporter by HIF-la:Targeting G6PT with mumbaistatin analogs in hypoxic mesenchymal stromal[J].Stem Cells,2009,27(3):489-497.
[17]Hu X,Yu SP,Fraser JL,et al.Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis[J].J Thoracic Cardiovasc Surg,2008,135(4):799-808.
[18]Brent R.Weil,Troy A. Markel, Jeremy L.Herrmann.Mesenchymal stem cells enhance the viability and proliferation of human fetal intestinal epithelial cells following hypoxic injury via paracrine mechanisms[J].Surgery,2009,146(2):190-197.
[19]D'Ippolito G,Diabim S,Howard GA,et al.Low oxygen tension inhibits Osteogenic differen-tiation and enhances sternness of human MIAMI cells[J].Bone,2006,39(3):513-522.
[20]Rochefort GY,Delorme B,Lopez A,et al.Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia[J].Stem Cells,2006,24(10):2202-2208.
[21]Covello KL, Kehler J, Yu H, et al.HIF-2 regulates Oct-4:effects of hypoxia on stem cell function, embryonic development,and tumor growth[J].Genes Dev,2006(5),20:557-570.
[22]Grayson WL,Zhao F, Izadpanah R,et al.Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs[J]J Cell Physiol,2006,207(2):331-339.
[23]Bosch P, Pratt SL,Stice SL.Isolation,characterization,gene modification.And nuclear repro-gramming of porcine mesenchymal stem cells[J].Biol Reprod,2006,74(1):46-57.
[24]Lin Q,Lee YJ,Yun Z.Differentiation arrest by hypoxia[J].J Biol Chem,2006,281(41):30678-30683.
[25]D'Ippolito QDiabim S,Howard GA,etal.Low oxygen tension inhibits Osteogenic differentiation and enhances sternness of human MIAMI cells[J].Bone,2006,39(3):513-522.
[26]Lennon DP,Edmison JM,Caplan AI.Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension:effects on in vitro and in vivo osteochondrogenesis[J].J Cell Physiol, 2001,187(3):345-355.
[27]Xie XJ,Wang JA,Cao J,Zhang X.Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions[J].Acta Pharmacol Sin,2006,27(9): 1153-1158.
[28]Moussavi-Harami F,Duwayri Y,Martin JA,et al.Oxygen effects on senescence in chondrocytes and mesenchymal stem cells:consequences for tissue engineering[J].Iowa Orthop J,2004,24:15-20.
[29]Droge W.Free radicals in physiologicall control of cell function[J].Physiol Rev,2002,82(1):47-95.
[30]朱斌,顾春虎,宿学家,等.低氧对大鼠骨髓间质干细胞的影响[J].中国现代医生,2009,47(2)：34-36.
[31]须珏华,周燕,谭文松.低氧促进兔骨髓间充质干细胞增殖[J].基础医学与临床,2008,28(12)：1239-1242.
[32]李海生,陈金武,朱玲玲,等.持续低氧增强人骨髓间充质干细胞体外增殖[J].基础医学与临床,2005,25(3)：268-271.
[33]Yonghui Jin, Tomohisa Kato, Moritoshi Furu,et al. Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase[J].Biochemical and Biophysical Research Communications,2010,391(3):1471-1476.
[34]Genbacev O, M.C.Simon,R. Johnson.:The biology of hypoxia:the role of oxygen sensing in development,normal function,and disease[J].Genes Dev,2004,18(18):2183-2194.
[35]Genbacev,O,Y Zhou,J.W:Ludlow,et al.Regulation of human placental development by oxygen tension[J].Science1997,277(5332):1669-1672.
[36]Schipani,E.,H.E.Ryan,S.Didrickson,et al.Hypoxia in cartilage:HIF-1 is essential for chondrocyte growth arrest and survival[J].Genes Dev,2001,15(21):2865-2876.
[37]Studer L,Csete M,Lee SH,et al.Enhanced proliferation,survival,and dopaminergic differenti-ation of CNS precursors in lowered oxygen[J].J Neurosei,2000,20(19):7371-7383.
[38]Yun Z.,H.L.Maecker,R.S.Johnson,et al.Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stral3:a mechanism for regulation of adipogenesis by hypoxia[J].Dev Cell,2002,2(3):331-341.
[39]Silver IA. Measurement of pH and ionic composition of pericellular sites[J].Philos Trans R Soc Lond B Biol Sci,1975,271(912):261-272.
[40]Wang DW; Fermor B,Gimble JM,et al.Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells[J].J Cell Physiol.2005,204(1):184-91.
[41]Kanichai M, Ferguson D, Prendergast PJ,et al. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells:a role for AKT and hypoxia-inducible factor (HIF)-l alpha[J]. J Cell Physiol,2008,216(3):708-715
[42]Wasim S. Khan, Adetola B. Adesida, Simon R. Tew,et al.Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions[J].Journal of Orthopaedic Research,2010,28(6):834-840.
[43]MalladiP,Xu Y,Chiou M,Giaccia AJ,et al.Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells[J].Am J Cell Physiol,2006,290(4):1139-1146.
[44]Kanichai M,Ferguson D,Prendergast PJ,et al.Hypoxia promotes chondrogenesis in rat mesen-chymal stem cells:a role for AKT and hypoxia-inducible factor (HIF)-la[J].J Cell Physiol, 2008,216(3):708-715.
[45]Martin-Rendon E,Hale SJ,Ryan D,et al.Transcriptional profiling of human cord blood CD133+ and cultured bone marrow mesenchymal stem cells in response to hypoxia[J].Stem Cells,2007,25(4): 1003-1012.
[46]Tondevold E, Eriksen J, Jansen E. Observation on long bone medullary pressures in relation to arterial PO2, PCO2, and pH in the anesthetized dog[J]. Acta Orthop Scand,1979,50:645.
[47]Grant JL,Smith B. Bone marrow gas tensions, bone marrow blood flow and erythropoiesis in man[J].Ann Int Med,1963,58:801-809.
[48]Kofoed H, Sjontoft E, Siemssen SO,et al. Bone marrow circulationafter osteotomy:Blood flow PO2, CO2, and pressure studied in dogs[J]. Acta Orthop Scand,1985,56(5):400-403.
[49]Maniatopoulos C,Sodek J,Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats[J]. Cell Tissue Res,1988,254 (2):317-330.
[50]Volkmer E, Kallukalam BC, Maertz J, et al.Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation[J].Tissue Eng Part A,2010,16(1):153-164.
[51]Lee JH,Kemp DM.Human adipose-derived stem cells display myogenic potential and perturbed function in hypoxic conditions[J].Biochem Biophys Res Commun,2006,341(3):882-888.
[52]Ali Salim, Randall P. Nacamuli, Elise F. Morgan,et al. Transient Changes in Oxygen Tension Inhibit Osteogenic Differentiation and Runx2 Expression in Osteoblasts[J].The Journal of Biological Chemistry,2004,279(38):40007-40016.
[53]Potier E, Ferreira E, Andriamanalijaona R,et al. Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression[J]. Bone,2007,40(4):1078-1087.
[54]Fink T, Abildtrup L,Fogd K,et al.Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia[J].Stem Cells,2004,22(7):1346-1355.
[55]Hongying Ren,Ying Cao,Qinjun Zhao,et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions [J]. Biochemical and Biophysical Research Communications, 2006,347(1):12-21.
[56]Utting JC.Robins SP,Brandao-Burch A,et al.Hypoxia inhibits the growth,differantiation and bone forming capacity of rat osteoblasts[J].Experimental Cell Research[J].2006,312(10):1693-1702.
[57]Zhou S,Lechpammer S,Greenberger JS,et al. Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling[J].J Biol Chem,2005,280(24):22688-22696.
[58]Kopen GC,Prokop DJ,Phinney DQet al. Marrow stromal cells migrate through out for brain and cerebellum,and they differentiate into astrocytes after injection into neonatal mouse brain[J]. Proc Natl Acad Sci USA,1999,96(19):10711-10716.
[59]Esneault E,Pacary E,Eddi D,et al. Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab,2008,28(9):1552-1563.
[60]Pacary E, Legros H,Bernaudin M,et al. Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells[J]. J Cell Sci.2006,119(13):2667-2678.
[61]Annabi B, Lee Y, Turcotte S.et al.Hypoxia promotes murine bone marrow-derived stromal cell migration and tube formation[J].Stem Cells,2003,21(3):337-347.
[62]Kaiming Liu,Luxiang Chi,Liang Guo,et al. The interactions between brain microvascular endothelial cells and mesenchymal stem cells under hypoxic conditions[J].Microvascular Research,2008,75(1):59-67.
[63]Rosova I,Dao M,Capoccia B,et al.Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells[J].Stem Cells,2008,26(8): 2173-2182.
[64]Xiao-jie XIE, Jian-an WANG, Jiang CAO,et al.Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions[J].Acta Pharmacologica Sinica,2006,27(9):1153-1158.
[65]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J].J Biol Chem,2006,281(22):15554-15563.
[66]Radini DJ.Gurtner GC.Homing to hypoxia:HIF-1 as a mediator of progenitor cell recruitment to injured tissue[J]. Trends Cardiovasc Med,2005,15(2):57-63.
[67]Zhu H,Mitsuhashi N,Klein A,et al.The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix[J].Stem Cells,2006,24(4):928-935.
[68]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1 [J].J Biol Chem,2006, 281(22):15554-15563.
[69]Bhakta S,Hong E,Koc O.The Surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell derived factor-1 in vitro but does not decrease apoptosis under Serum deprivation[J]. Cardiovasc Revasc Med,2006,7(1):19-24.
[70]Sun-Young Ju, Kyung-Ah Cho, Su Jin Cho,et al.Effect of hypoxic treatment on bone marrow cells that are able to migrate to the injured liver[J].Cell Biology International,2009,33(1):31-35.
[71]王心蕊,何旭,王医术,等.低氧促进人骨髓间充质干细胞迁移的实验研究[J].中国免疫学杂志,2006,22(12)：1100-1102.
[72]朱洁,周竹娟,龚自力,等.低氧对人骨髓间充质干细胞趋化因子受体CXCR4和CX3CR1表达的影响[J].中国组织工程研究与临床康复,2009,13(23)：4485-4489.
[73]Stellos K, Langer H, Daub K,et al. Platelet-Derived Stromal Cell Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells[J].Circulation,2008,117(2):206-215.
[74]Ramirez-Bergeron DL, Simon MC.Hypoxia-inducible factor and the development of stem cells of the cardiovascular system[J]. Stem Cells,2001,19(4):279-286.
[75]Csete M.Oxygen in the cultivation of stem cells[J].Ann N Y Acad Sci,2005,1049:1-8.
[76]Harris AL.Hypoxia-a key regulatory factor in tumour growth[J].Nat Rev Cancer,2002,2(1):38-47.
[77]Esteban MA,Tran MQHarten SK,et al.Regulation of E-cadherin expression by VHL and hypoxia-inducible factor [J]. Cancer Res,2006,66(7):3567-3575.
[1]耿长山.黄芪的免疫药理作用研究[J].中西医结合杂志,1986,3(1)：62
[2]耿长山,等.黄芪多糖对去T细胞小鼠促进抗体产生机理探讨[J].中国药理通讯,1985,2(2)：14.
[3]陈丽娟.黄芪多糖对小鼠吞噬能力的影响[J].中国药理学报,1981,2(3)：20.
[4]翁玲,刘彦,刘学英,等.黄芪多糖粉针剂对小鼠脾细胞分泌细胞因子及NK杀伤能力的影响[J].中医药学刊,2003,21(9)：1522-1524.
[5]钟国赣,孙晓霞,李云义,等.黄芪皂甙对离体工作心脏的强心作用[J].白求恩医科大学学报,1994,20(5)：448.
[6]石刚刚,陈锦香,李长潮,等.黄芪注射液对冠状动脉直接作用的研究[J].中药新药与临床药理,1999,10(1)：38.
[7]梁明,韩竹梅,梁小光,等.黄芪冻干粉对大鼠离体心脏的作用[J].中草药,2000,31(11)：846-847.
[8]何蕾,江朝光,.黄芪注射液抗心肌细胞再灌注损伤的作用及机制[J].世界急危重病医学杂志,2006,3(4)：1365-1366.
[9]王曦,孟巍,荆洪英.黄芪注射液治疗冠心病心绞痛的临床疗效观察[J].黑龙江医药科学,2004,27(4)：76-77.
[10]徐西.党参、黄芪对血小板聚集的临床及实验研究[J].中药药理与临床,1985,4(4)：32.
[11]高建,徐先祥,徐先俊,等.黄芪总皂甙抗血栓形成作用实验研究[J].中成药,2002,24(2)：116-118.
[12]侯世荣.黄芪口服液治疗慢性肝炎的疗效观察[J].中草药,2000,31(10)：766.
[13]李智军,魏连波,贺丰,等.黄芪多糖治疗大鼠系膜细胞增生性肾炎的实验研究[J].中国中西医结合肾病杂志,2000,1(4)：206.
[14]张英,李铁兵,孙茂波.参芪合剂抗疲劳作用的基础与临床研究[J].中医药学报,1998,26(4)：35.
[15]李卫平,明亮,张艳,等.黄芪多糖耐缺氧作用的实验研究[J].安徽医科大学学报,1995,30(3)：184.
[16]余勤,罗依,董勤,等.黄芪对间质干细胞分化为神经元样细胞的定向诱导作用[J].中华急诊医学杂志,2004,13(12)：826-829.
[17]王勇,陆长青,王凡.黄芪诱大鼠骨髓间充质干细胞分化为神经样细胞的研究[J].解剖学杂志,2006,14(1)：5-8.
[18]王新生,赵荧,李海峰,等.黄芪诱导大鼠骨髓间充质干细胞的分化特点[J].中国组织工程研究与临床康复,2009,13(19)：3785-3789.
[19]王新生,李海峰,赵荧,等.黄芪诱导大鼠骨髓间充质干细胞分化早期胞内钙调蛋白mRNA的转录水平[J].中国组织工程研究与临床康复,2009,13(23)：4495-4499.
[20]Li ZS, Pham TD, Tam ir H, et al. Enteric dopaninergic neurons:definiation, developmental lineage, and effects of extrinsic denerwation[J]. J Neuro sci,2004,24(6):1330-1339.
[21]董晓先,冷水龙,刘金保.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞的基因表达谱[J].中国临床康复,2006,10(21)：1-3.
[22]Smolich BD, Papkoff J. Regulated expression of Wnt family member during neuroectodermal differentiation of P19 embryonal carcinoma cells overexp ression of Wnt-1 pertubs normal differentiation-specific propertiea[J]. Dev Biol,1994,166(1):300-310.
[23]Nusse R, Varmus HE. Wnt genes[J]. Cell,1992;69(7):1073-1087.
[24]Parr BA, Shea MJ, Vassileva G, et al. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds[J]. Development,1993,119(1):247-261.
[25]Hamada-Kanazawa M, Ishikawa K, Nomo to K. Sox 6 overexpression causes cellular aggregation and the neuronal differentiation of P19 embryonic carcinoma cells in the absence of retinoic acid[J]. FEBS Lett,2004:560 (13):192-198.
[26]杨新文,王勇.黄芪诱导大鼠骨髓间充质干细胞分化为神经样细胞[J].中国组织工程研究与临床康复,2008,12(25)：4996-5000.
[27]王新生,崔慧先,刘华,等.黄芪诱导骨髓间充质干细胞分化进程中细胞内钙离子浓度的动态变化[J].中国组织工程研究与临床康复,2007,11(42)：8469-8472.
[28]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2007,24(1)：37-40.
[29]杨庆有,冼绍祥,孙慧茹,等.黄芪含药血清诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].辽宁中医杂志,2008,35(6)：832-834.
[30]杨博华,朱陵群,张娟子,等.黄芪、三七促进骨髓干细胞体外转化并扩增血管内皮前体细胞(EPC)作用的研究[J].中国中药杂志,2005,30(22)：1761-1763.
[31]邹萍,胡翔,刘德伍.黄芪诱导人骨髓间充质干细胞向表皮样细胞的分化[J].中国组织工程研究与临床康复[J],2009,13(36)：7099-7102.
[32]许春姣,郭峰,高清平,等.骨髓基质干细胞与黄芪-壳聚糖／聚乳酸支架对犬牙周骨缺损再生的影响[J].中南大学学报(医学版),2006,31(4)：512-517.
[33]杨云华,于小华,李双杰,等.黄芪注射液对多柔比星诱导的脐血间充质干细胞凋亡的影响[J].实用儿科临床杂志.2009,24(11)：851-854.
[34]石田寅夫,王秀云,柴丽娟,等.体外培养胚胎神经干细胞的增殖及中药有效成分对其增殖能力的影响[J].天津中医药,2009,26(2)：155-159.
[35]刘建军,姚忠祥,秦茂林,等.单昧黄芪红花丹参注射液对神经干细胞分化影响的初步研究[J].第三军医大学学报,2006,28(14)：1470-1472.
[36]刘静,罗雪,钟善传,等.黄芪皂甙诱导小鼠神经干细胞向神经元分化.第四军医大学学报[J],2009,30(7)：580-583.
[37]张艳军,范祥,胡利民,等.不同治则中药单体对体外培养神经干细胞分化的影响[J].天津中医药,2004,21(2)：156-157.
[38]Gaugler MH,Squiban C,Claraz M,et al. Characterization of the response of human bone marrow endothelial cells to in vitro irradiation[J].Bri J Haemat,1998,103(4):980-989.
[39]刘晓,武正炎,范萍.黄芪在外周血造血干细胞移植中应用的初步实验研究[J].镇江医学院学报,2001,11(1)：15-17.
[40]许勇,杨代耘,钟亚琴,等.复方黄芪注射液对小鼠多能造血干细胞(CFU-S)影响的实验研究[J].四川省卫生管理干部学院学报,1995,14(1)：1-2
[41]Fennie C, Cheng J, Dowbenko D,et al.CD34+endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors [J]. Blood,1995,86(12):4454-4467.
[42]Sansilvestri P, Cardoso AA,Batard P, et al. Early CD34 high cells can be separated into KIT high cells in which transforming growth factor-beta[TGF-beta] down modulates c-kit and KIT low cells in which anti-TGF-beta up modulates c-kit[J].Blood,1995,86(5):1729-1735.
[43]Huang E, Nocka K, Beier DR,et al.The Hematopoietic Growth factor KL is encoded by the S/locus and is the ligand of the c-kit receptor,the gene product of the W locus[J].Cell,1990,63(1):225-233.
[44]Zsebo KM,Wypych J,McNiece IK, et al.Identification,purification,and biological characteriza-tion of hematopoietic stem cell factor from buffalo rat live-conditioned medium[J].Cell,1990, 63(1):195-201.
[45]Nishi N,Ishikawa R,Inoue H, et al. Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line[J].Exp Hematol,1996,24(11):1312-1321.
[46]李玛琳,Cardoso AA,Hatzfeld A,等.SCF和TGF-β反义寡核苷酸对CD34+造血细胞的协同作用[J].实验血液学杂志,1996,4(3)：252-256.
[47]祝晓玲,祝彼得.黄芪体外作用对贫血小鼠骨髓基质细胞分泌SCF的影响[J].细胞与分子免疫学杂志,2002,18(4)：396-398.
[48]刘德伍,胡翔,刘德明.黄芪诱导表皮干细胞增殖构建组织工程皮肤治疗皮肤缺损[J].中药药理与临床,2004,20(5)：16-18.
[49]胡翔,邹萍,刘莉玲,等.黄芪对人皮肤表皮干细胞增殖活性的影响[J]中国组织工程研究与临床康复,2009,13(19)：3689-3692.
[50]王蕾,张科伟,赵大伟,等.MTT法检测黄芪和丹参对人乳腺干细胞体外增殖的影响[J].中国组织工程研究与临床康复,2008,12(8)：1418-1421.
[1]Asahara T,Murohara T,Sullivan A,et al.Isolation of putative progenitor endotheial cells for angiogensis[J].Science,1997,27(5):964-967.
[2]赵春华.干细胞原理、技术与临床.北京：化学工业出版社,2006：3-14；173-174.
[3]Asahara T,Murohara T,Takahashi T,et al.Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].Circ Res,1999;85(3):221-228.
[4]Bussolino F,Mantovani A,Persico G.Molecular mechanism of blood vessel formation[J].Trends Biochem Sci,1997,22(7):251-256.
[5]Yamamoto K,Knodo T,Suzuki S,et al.Molecular evaluation of endothelial progenitor cells in Patiens with ischemic limbs:therapeutic effects by stem Cell trans-plantation[J].Arterisclser Thromb Vasc Bilo,.2004,24(12):192-196.
[6]Pugh CW,Ratccliffe PJ.Regulation of angiogenesis by hypoxia:role of the HIF system[J].Nat Med,2003,9(6):677-684.
[7]Carmeliet P.Angiogenesis in health and disease[J].Nat Med,2003,9(6):653-660.
[8]Li W W,Talcott K E,Zhai A W,et al.The Role of Therapeutic Angiogenesis in Tissue Repair and Regeneration[J].Adv Skin Wound Care,2005,18(9):491-500.
[9]Mazure NM,Brahimi-Horn MC,Pouyssegur J.Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis[J].Curr Pharm Des,2003,9(7):531-541.
[10]Gale NW,Yancopoubs GD.Growth factors acting via endothelial cell specific receptor tyrosine kinases:VEGF's,angiopoietins,and ephrins in vascular development[J].Genes Dev,1999,13(78): 1055-1066.
[11]Thurston G, Rudge JS,Ioffe E,et al.Angiopoietin-1 protects the adult vasculature against plasma leakage[J]. Nat Med,2000,6(36):460-463.
[12]Hirschi K, Rohovsky S,D'Amore P.PDGF,TGF-b and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate[J].J Cell Biol,1998,141(3):805-814.
[13]Fromherz P,Schaden H,Vetter T.Guided outgrowth of leech neurons in culture[J].Neurosci Lett, 1991,129(1):77-80.
[14]Horbert CB,Mclernon TL,Hypolite CL,et al.Micropatterning gradlents and controlling surface densities of photoactivatable biomolecules on self-assembled monolayers of oligo(ethylene glycol)alkanethiolates[J].Chem Biol,1997,4(10):731-773.
[15]杨博华,秦建辉,朱陵群,等,自体骨髓干细胞移植与中药合用治疗下肢缺血性病变[J].北京中医药大学学报,2004,27(6)：76-78.
[16]杨博华,秦建辉,朱陵群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683-684.
[17]杨博华,张娟子,朱陵群,等.黄芪、三七对下肢缺血患者骨髓干细胞体外分化作用的影响[J].中医杂志,2007,48(11)：994-995.
[1]Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell:entity or function? [J].Cell,2001,105(7):829-841.
[2]Traycoff CM, Abboud MR, Laver J,et al. Evaluation of the in vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells[J].Exp Hematol,1994,22 (2):215-222.
[3]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J]. Science,1999,284(5411):143-147.
[4]Wakitani S, Saito T, Caplan Al.Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine[J].Muscle nerve,1995,18(12):1417-1426.
[5]Reyes M,Lund T,Lenvik T,et al.Purifccation and ex vivo expansion of postnatal human marrow nesodermal progenitor cell[J].Blood,2001,98(9):2615-2625.
[6]Sanchez Ronos J.Song S,Cardozo Pelaez F,et al.Adult bone marrow strorml cells differentiate into neural cells in vitro[J].Exp Neurol,2000,164(2):247-256.
[7]赵春华.干细胞原理、技术与临床.北京：化学工业出版社,2006：3-14；173-174.
[8]Schattmnan GC,Dunnwald M,Jiao CHH. Biology of bone marrow-derived endothelial cell precursors[J].Am J Physiol Heart Circ Physiol,2007,292(1):1-18.
[9]Krause DS,Theise ND,Collector MI,et al.Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cells. Cell,2001,105(3):369-377.
[10]Kotton DN, Ma BY, Cardoso WV, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium[J]. Development,2001,128(24):5181-5188.
[11]Satoshi Gojo,Noriko Gojo, Yukiji Takeda,et al.In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells[J]. Experimental cell research,2003,288(1):51-59.
[12]Liu, J.W. et al. Characterization of endothelial-like cells derived from human mesenchymal stem cells[J]. J.Thromb.Haemost,2007,5(4):826-834.
[13]Soonpaa,M.H.,et al,Formation of nascent intercalated disks between grafted fetal cardiomyo-cytes and host myocardium[J]. Science,1994.264(5155):98-101.
[14]Ferrara N,Davis-Smyth T. The biology of vascular endothelial growth factor[J]. Endocr,1997, 18(1):4-25.
[15]Benjamin LE,Golijanin D,Itin A,et al. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor with drawal[J].Clin Invest,1999,103(2):159-165.
[16]Oswald, J., Boxberger, S.,Jorgensen,B.,et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro[J]. Stem Cell,2004,22(3):377-384.
[17]Gang Zhang,Jianye Zhoub, Quanxin Fana, et al.Arterial-venous endothelial cell fate is related to vascular endothelial growth factor and Notch status during human bone mesenchymal stem cell differentiation[J]. FEBS Letters,2008,582(19):2957-2964.
[18]Klopper T,et al.High efficient adenoviral-mediated VEGF and Ang-1 gene delivery into osteogenically differentiated human mesenchymal stem cells[J].Microvasc Res,2008,75(l):83-90.
[19]Reyes M,Dudek A, Jahagirdar B, et al. Origin of endothelial progenitors in human postnatal bone marrow[J]. J Clin Invest,2002,109(3):337-346.
[20]Annabi B, Lee Y, Turcotte S.et al.Hypoxia promotes murine bone marrow-derived stromal cell migration and tube formation[J].Stem Cells,2003,21(3):337-347.
[21]Kaiming Liu,Luxiang Chi,Liang Guo,et al. The interactions between brain microvascular endothelial cells and mesenchymal stem cells under hypoxic conditions[J].Microvascular Research,2008,75(1):59-67.
[22]Ivana Rosova, Mo Dao, Ben Capoccia,et al.Hypoxic Preconditioning Results in Increased Motility and Improved Therapeutic Potential of Human Mesenchymal Stem Cells[J].Stem Cells,2008,26(8):2173-2182.
[23]Ke QD, Costa M Hypoxia Inducible Factor-1(HIF-1) [J].Mol Pharmacol, 2006,70(5):1469-1480.
[24]Semenza CL.O2-regulated gene expression:transcriptional control of cardiorespiratory physiolog by HIF-1[J].J Appl Physiol,2004,96(3):1173-1177.
[25]Lee J W,Bae SH, Jeong J W,et al.Hypoxia inducible factor alpha(HIF-1):its protein stability and biological functions[J].Exp Mol Med,2004.36(1):1-12.
[26]Wang GL,Semenza GL. Characterization of DNA clincling activity by hypoxia of hypoxia inducible factor-1 and regulationgof DNA clincling activity by hypoxia[J].Biol Chem,1993,268 (29):21513-21518.
[27]Brat DJ,Castellano-Sanchez AA.,Hunter SB,et al.Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population[J]. Cancer Res,2004,64(3):920-927.
[28]Semenza CxL. Hypoxia-inducible factor 1:oxygen homeostasis and disease pathophysiology[J]. Trends Mol Med,2001,7(8):345-350.
[29]Brat, D.J., Mapstone, T.B. Malignant glioma physiology:cellular response to hypoxia and its role in tumor progression[J]. Ann Intern Med,2003,138(8):659-668.
[30]Li J,Sh worak N.W,Simons M.Increased reponsiveness of hypoxic endothelial cell to FGF2 is mediated by HIF-lalpha-dependent r egulation of enzymes involved in synthesis of heparin sulfate FGF2-binding sites[J].Cell Sci,2002,115(9):195.
[31]Sun YJ, Jin k,Xie L.VEGF-induced neuroprotection,neurogenesis,and Angiogengsis after focal cerebral ischema[J].J Clin invest,2003,111(12):1843-1851.
[32]Chavez JC,Agani F,Pichiule P.Expression of hypoxic inducible factor-1 in the brain of rats during chronic hypoxia[J].J Appl Physiol,2000,89(5):1937-1942.
[33]Dai Y,Xu M,Wang Y, et al.HIF-lalpha induced-VEGF over expression in bone marrow stem cells protects cardiomyocytes againstischemia[J].J Mol Cell Cardiol,2007,42(6):1036-1044.
[34]D' Ippolito QDiabira S,Howard GA,et al.Low oxygen tension inhibits osteogenic differenti-ation and enhances sternness of human MIAMI cells[J].Bone,2006;39(3):513-522.
[35]Volkmer E, Kallukalam BC, Maertz J, et al.Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation[J].Tissue Eng Part A,2010,16(1):153-164.
[36]熊迎春,洪小平,陈泽斌,等.黄芪对实验性糖尿病大鼠血管内皮细胞形态的影响[J].中医药学刊,2004,22(10),1859.
[37]谢席胜,黄宗文,李秀钧,等.黄芪对高葡萄糖、游离脂肪酸培养的人血管内皮细胞一氧化氮含量的影响[J].中国临床康复,2004,8(30)：6683.
[38]李绚,阎蓉华,罗照田,等.黄芪注射液对人脐静脉血管内皮细胞的增殖作用[J].华西药学杂志,2005,20(1)：48.
[39]雷燕,高倩,李悦山,等.黄芪、当归及其组方促血管内皮细胞增殖作用的研究[J].中国中西医结合杂志,2003,23(10)：753.
[40]哈敏文,李振,何安光.黄芪合剂防止化疗性骨髓抑制的实验研究[J].中国医科大学学报1997；26(5)：449-452.
[41]阙华发,朱元颖,王云飞,等.益气化瘀中药对糖尿病皮肤溃疡大鼠缺氧诱导因子-1α和血管内皮细胞生长因子的影响[J].中西医结合学报,2007,5(2)：165-169.
[42]余勤,罗依,董勤,等.黄芪对间质干细胞分化为神经元样细胞的定向诱导作用[J].中华急诊医学杂志,2004,13(12)：826-829.
[43]王新生,赵荧,李海峰,等.黄芪诱导大鼠骨髓间充质干细胞的分化特点[J].中国组织工程研究与临床康复,2009,13(19)：3785-3789.
[44]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究[J].广州中医药大学学报,2007,24(1)：37-40.
[45]邹萍,胡翔,刘德伍.黄芪诱导人骨髓间充质干细胞向表皮样细胞的分化[J].中国组织工程研究与临床康复[J],2009,13(36)：7099-7102.
[46]杨博华,秦建辉,朱陵群等,自体骨髓干细胞移植与中药合用治疗下肢缺血性病变[J].《北京中医药大学学报》,2004,27(6)：76-78.
[47]杨博华,秦建辉,朱陵群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683-684.
[48]杨博华,张娟子,朱陵群,等.黄芪、三七对下肢缺血患者骨髓干细胞体外分化作用的影响[J].中医杂志,2007,48(11)：994-995.
[1]Kucia M,RatajcZak J,Reca R,et al.Tissue-specific muscle,neural and liver stem/progenitor cells reside in the bone marrow,respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury [J].Blood cells Mol Dis,2004,32(1):52-57.
[2]Mastsen FA,et al. The relationship of transcutaneous PO2 and laser-Doppler measurement in a human model of local arterial insufficiency[J].Surg Gynecol Obstet 1984,159(5):418-422.
[3]De Falco E, Porcelli D, Torella AR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells[J]. Blood.2004,104(12):3472-3482.
[4]Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture[J].Leukemia,2003,17(1):160-170.
[5]Ruster B, Gottig S, Ludwig RJ, et al. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells[J].Blood,2006,108(12):3938-3944.
[6]Shih YR, Chen CN,Tsai SW, et al.Growth of mesenchymal stem cells on electrospun type I collagen nanofibers[J].Stem Cells,2006,24(11):2391-2397.
[7]Phinney DQ Baddoo M, Dutreil M, et al. Murine mesenchymal stern cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration[J]. Stem Cells Dev,2006,15(3):437-447.
[8]Hur J,Yoon CH,Lee CS,et al.Akt is a key modular of endothelial progenitor cell trafficking in ischemic muscle[J].Stern Cells,2007,25 (7):1769-1778.
[9]Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34+cell on vascular endothelium under shear flow. J Clin Invest,1999,104(9):1199-1211.
[10]Peled A, Petit I, Kollet O,et al.Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4[J].Science,1999; 283(5403):845-848.
[11]Mohle R,Bautz F, Rafii S. et al.The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor 1 [J]. Blood,1998,91(12):4523-4530.
[13]Hiasa K, Ishibashi M, Ohtani K, et al.Gene transfer of stromal cell-derived factor-I alpha enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/ endothelial nitric oxide synthase-related pathway:next-generatian chemokine therapy for therapeutic neovasculorization[J]. Circulation,2004,109(20):2454-2461.
[13]Yamaguchi J, Kusano KF, Masuo O,et al.Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cells recruitment for ischemic neovascularizatian[J].Circulation. 2003,107(9):1322-1328.
[14]Aiuti A, Webb U, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood[J].J Bxp Med.1997,185(1):111-120.
[15]Togel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms[J].Am J Physiol Renal Physiol, 2005,289(1):31-42.
[16]Ponte AL,Marais E,Gallay N,et al.The in vitro migration capacity of human bone marrow mesenchymal stem cells:comparison of chemokine and growth factor chemotactic activities [J]. Stem Cells,2007,25(7):1737-1745.
[17]Shi M,Li J,Liao L,et al.Regulation of CXCR4 expression in human mesenchymal stem cells by cytolcine treatment:role in homing efficiency in NOD/SCID mice [J]. Haematologica,2007,92(7): 897-904.
[18]Askari AT, Unzek S, Popvic ZB, et al. Effect of stromal cell-derived factor-1 on stem cell homing and tissue regeneration in ischemic cardiomyopathy[J].Lancet,2003,362(9385):697-703.
[19]Ceradini D, Kalkarni A, Callaghan M, et al.Progenitor cell tracking is regulated by hypoxic gradients through HIF-1 induction of SDF-1 [J]. Nat Med,2004,10(8):858-864.
[20]De Falco E, PorceV P, Torella AR, et al, SDF-1 involvement in endothelial phenotype and ischemio-induced recruitment of bone marrow progenitor cells[J].Blood,2004;104(12):3472-3482.
[21]Le Y, Honczarenko M,Glodek AM, et al. CXC chemokine ligand 12-induced focal adhesion kinase activation and segregation into membrane domains is modulated by regulator of G protein signaling 1 in pro-B cells [J].J Immunol,2005,174(5):2582-2590.
[22]Katayama A, Ogino T, Bandoh N, et al. Expression of CXCR4 and its down-regulation by IFN-gamma in head and neck squamous cell carcinoma [J].Clin Cancer Res,2005,11(8):2937-2946.
[23]Wright LM, Maloney W, Yu X, et al. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts [J].Bone,2005,36(5):840-853.
[24]Abbott JD, Huang Y, Liu D, et al. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J]. Circulation,2004,110(21):3300-3305.
[25]Ye Wang, Yubin Deng, Guang-Qian Zhou.SDF-lalpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model [J].Brain Research,2008,1195:104-112.
[26]Thieme, S.,Ryser, M.F., et al..Stromal cell derived factor-1 alpha directed chemoattraction of transiently CXCR4 overexpressing bone marrow stromal cells into functionalized three-dimensional biomimetic scaffolds.Tissue Eng.2009,15(4):687-696.
[27]Xuezhong He, Junyu Ma, Esmaiel Jabbari-Migration of marrow stromal cells in response to sustained release of stromal-derived factor-la from poly(lactide ethylene oxide fumarate) hydrogels.International Journal of Pharmaceutics,2010,390(2):107-116.
[28]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J].J Biol Chem,2006,281(22):15554-15563.
[29]Radini DJ.Gurtner GC.Homing to hypoxia:HIF-1 as a mediator of progenitor cell recruitment to injured tissue[J].Trends Cardiovasc Med,2005,15(2):57-63.
[30]Zhu H,Mitsuhashi N,Klein A,et al.The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix[J].Stem Ceils,2006,24(4):928-935.
[31]Okuyma H,Balaji Krishnamachary,Yi Fu Zhou,et al.Expression of vegf receptor lin bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1[J]. J Biol Chem,2006,281(22):15554-15563.
[32]Bhakta S,Hong E,Koc O.The Surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell derived factor-1 in vitro but does not decrease apoptosis under Serum deprivation[J]. Cardiovasc Revasc Med,2006,7(l):19-24.
[33]Sun-Young Ju, Kyung-Ah Cho, Su Jin Cho,et al.Effect of hypoxic treatment on bone marrow cells that are able to migrate to the injured liver [J]. Cell Biology International,2009,33(1):31-35.
[34]王心蕊,何旭,王医术,等.低氧促进人骨髓间充质干细胞迁移的实验研究[J].中国免疫学杂志,2006,22(12)：1100-1102.
[35]朱洁,周竹娟,龚自力,等.低氧对人骨髓间充质干细胞趋化因子受体CXCR4和CX3CR1表达的影响[J].中国组织工程研究与临床康复,2009,13(23)：4485-4489.
[36]Stellos K, Langer H, Daub K,et al. Platelet-Derived Stromal Cell Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+Cells to Endothelial Progenitor Cells.Circulation,2008,117(2):206-215.
[37]欧阳长生,王云开,苏淘,等.丹参及血府逐瘀汤含药血清与兔骨髓间充质干细胞的体外迁移：促进还是抑制?[J].中国组织工程研究与临床康复,2009,13(40)：7847-7851.
[38]郭国庆,沈伟哉,钟世镇.丹参素和丹酚酸对胎鼠脑神经干细胞迁移的诱导[J].中国组织工程研究与临床康复,2007,11(7)：1225-1228.
[39]张芙荣,陈君柱,朱军慧,等.葛根素对外周血内皮祖细胞数量和功能的影响[J].中国中药杂志,2004,29(8)：777-781.
[40]王兴祥,尚云鹏,陈君柱,等.银杏叶提取物对外周血内皮祖细胞数量和功能的影响[J].药学学报,2004,39(8)：656-660.
[41]顾俊,王长谦,范华骅,等.白藜芦醇对外周血内皮祖细胞功能的影响[J].心脏杂志,2006,18(6)：617-621.