Neuroscience Research Center, Chongqing Medical University, Chongqing, 400016, China.
Curr Neurovasc Res. 2010 May;7(2):85-94. doi: 10.2174/156720210791184952.
Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent.
中风是全球第二大致死原因，也是美国和欧洲成年人残疾的首要原因。蛛网膜下腔出血（SAH）是中风的一种亚型，占每年所有中风的 7%，死亡率和发病率最高。已经有许多治疗干预措施用于治疗 SAH 后的脑损伤，但没有一种达到降低死亡率的临床有效性水平。人参皂苷 Rb1（GRb1）是中药人参的主要成分之一，已被证明通过抗细胞凋亡途径减少缺血性脑损伤和心肌损伤。在本研究中，我们研究了 GRb1 在大鼠蛛网膜下腔出血诱导的脑损伤中的应用。使用了四组：假手术组、载体组（SAH）、低剂量治疗组（SAH+5mg/kg GRb1）和高剂量治疗组（SAH+20mg/kg GRb1）。评估包括基底动脉壁厚度和平均横截面积，以评估脑血管痉挛；伊文思蓝外渗以评估血脑屏障（BBB）通透性；免疫组织化学和 Western blot 分析寻找特定的促凋亡标志物；以及隧道染色评估细胞死亡。此外，还研究了死亡率、神经功能和脑水肿。结果表明，高剂量 GRb1 治疗显著增大了基底动脉的平均横截面积，减小了壁厚度，降低了神经功能缺损、脑水肿、BBB 破坏和 TUNEL 阳性细胞表达。同时，我们发现 P53、Bax 和 Caspase-3 的蛋白表达显著降低，而 bcl-2 的表达在 Rb1 治疗中上调。这项研究的结果表明，GRb1 可以缓解脑血管痉挛，并可能为蛛网膜下腔出血患者提供神经保护。其潜在机制可能部分与抑制 P53 和 Bax 依赖性促凋亡途径有关。还需要更多的研究来证实这些结果，并确定其作为长期药物的潜力。
