Intravenous infusion of dihydroginseno side Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL
Intravenous infusion of dihydroginseno side Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL
复制标题
DOI：
10.1089/neu.2006.0182
复制
发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Hatai, Ryuji
中科院分区：
文献类型：
--
作者：
Sakanaka, Masahiro;Zhu, Pengxiang;Hatai, Ryuji
红参根（Panax Ginseng CA Meyer）已被许多亚洲人临床使用数千年，没有任何有害影响。红参根的主要成分之一是GRb-1（gRb 1）。以前，我们表明，静脉输注gRb 1改善缺血性脑损伤，通过上调的抗凋亡因子，BCI-X-L和局部应用gRb 1烧伤创面促进伤口愈合，通过上调血管内皮生长因子（VEGF）。在本研究中，我们生产了二氢吡喃Rb 1（dgRb 1），一种稳定的gRb 1的化学衍生物，并表明静脉输注dgRb 1可改善脊髓损伤（SCI）以及缺血性脑损伤。正如我们所预期的，dgRb 1的有效剂量比gRb 1低10倍。静脉输注该有效剂量的dgRh 1不会影响脑温、血压或脑血流量，这表明dgRh 1可以拯救受损的神经元而不影响全身参数。在随后的体外研究中，集中在dgRb 1诱导的基因产物的表达负责神经元死亡或存活，我们发现，dgRb 1不仅可以上调表达的BCI-XL，但也是一个强大的血管生成和神经营养因子，VEGF。我们还发现dgRb 1诱导的bcl-X-L和VEGF mRNA的表达分别是HRE（缺氧反应元件）和STRE（信号转导和转录激活因子5（Stat 5）反应元件）依赖的。
Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb-1 (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, BCI-X-L and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF). In the present study, we produced dihydroginsenoside Rb1 (dgRb1), a stable chemical derivative of gRb1, and showed that intravenous infusion of dgRb1 improved spinal cord injury (SCI) as well as ischemic brain damage. As we expected, the effective dose of dgRb1 was ten times lower than that of gRb1. Intravenous infusion of dgRb1 at this effective dose did not affect brain temperature, blood pressure or cerebral blood flow, suggesting that dgRb1 rescued damaged neurons without affecting systemic parameters. In subsequent in vitro studies that focused on dgRb1-induced expression of gene products responsible for neuronal death or survival, we showed that dgRb1 could upregulate the expression of not only BCI-XL, but also a potent angiogenic and neurotrophic factor, VEGF. We also showed that dgRb1-induced expression of bcl-X-L and VEGF mRNA was HRE (hypoxia response element) and STRE (signal transducers and activators of transcription 5 (Stat5) response element) dependent, respectively.