Department of Neurosurgery, Tang Du Hospital and Institute for Functional Brain Disorders, Xi'an 710032, PR China.
Neurochem Int. 2012 Apr;60(5):458-65. doi: 10.1016/j.neuint.2012.01.026. Epub 2012 Feb 8.
Inflammation injury plays a key role in the process of cerebral injury induced by ischemia/reperfusion (I/R). Thus, we studied the potential of astragaloside IV, one of the major and active components of the astragalus membranaceous, to protect rat against cerebral inflammation injury elicited by focal cerebral ischemia and reperfusion and related protective mechanisms. The rat model was induced by intraluminal occlusion of the right middle cerebral artery with reperfusion. Animals received astragaloside IV (10 or 20 mg/kg) injections when reperfusion was began to. Neurobehavioral evaluation and infarct assessment were studied. Myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The rates of CD11b/CD18-positive neutrophils were analyzed via flow cytometry. Intercellular adhesion molecule-1 (ICAM-1) and nuclear factor κB (NF-κB) were measured by immunohistochemistry and Western blot. Astragaloside IV improved neurological outcome and reduced infarct volume at 24 h after reperfusion. The protective effect was achieved by preventing neutrophils accumulation in the brain parenchyma demonstrated by significantly reducing the concentration of MPO in brain tissue. Astragaloside IV exerts the protection through remarkably decreasing the percentage of CD11b/CD18-positive neutrophils and down-regulating the expression of intercellular adhesion molecule-1 (ICAM-1), which is partly achieved by strongly attenuating the production of TNF-α and IL-1β and inhibiting level of nuclear factor-κB (NF-κB). We propose an anti-inflammatory mechanism evoked by astragaloside IV by suppression of neutrophils adhesion-related molecules, which exerts neuroprotection against I/R injury.
炎症损伤在缺血/再灌注（I/R）引起的脑损伤过程中起着关键作用。因此，我们研究了黄芪甲苷 IV（黄芪的主要和活性成分之一）对大鼠局灶性脑缺血再灌注引起的脑炎症损伤的潜在保护作用及其相关保护机制。通过管腔内阻塞右侧大脑中动脉再灌注诱导大鼠模型。当再灌注开始时，动物接受黄芪甲苷 IV（10 或 20mg/kg）注射。研究神经行为评估和梗塞评估。通过酶联免疫吸附试验（ELISA）测量髓过氧化物酶（MPO）和肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）。通过流式细胞术分析 CD11b/CD18 阳性中性粒细胞的比率。通过免疫组织化学和 Western blot 测量细胞间黏附分子-1（ICAM-1）和核因子 κB（NF-κB）。黄芪甲苷 IV 改善了再灌注后 24 小时的神经功能预后并减少了梗塞体积。通过显著降低脑组织中 MPO 的浓度来防止中性粒细胞在脑实质中的积累来实现保护作用。黄芪甲苷 IV 通过显著降低 CD11b/CD18 阳性中性粒细胞的百分比并下调细胞间黏附分子-1（ICAM-1）的表达来发挥保护作用，这部分是通过强烈抑制 TNF-α和 IL-1β的产生和抑制核因子-κB（NF-κB）的水平来实现的。我们提出了一种由黄芪甲苷 IV 引起的抗炎机制，通过抑制中性粒细胞黏附相关分子，对 I/R 损伤发挥神经保护作用。
