Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong Province, China.
Neurochem Res. 2013 Sep;38(9):1871-9. doi: 10.1007/s11064-013-1093-1. Epub 2013 Jun 19.
Ischemic stroke is the most common type of stroke and brings about a big disease burden because of high mortality and disability in China. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to possess anti-inflammatory and free radical scavenging effects and even regulate astrocyte activation, but the possible role of tetrandrine in ameliorating cerebral ischemia/reperfusion injury of ischemic stroke remains unknown. The aim of this study was to determine the effects of tetrandrine on neurological injury and differential proteomic changes induced by transient reversible middle cerebral artery occlusion (MCAO) in mice. Male Balb/c mice were divided into sham (n = 30), MCAO + saline as control (n = 30), and MCAO + Tet as tetrandrine-treated (n = 30) groups. Mice in the control and tetrandrine-treated groups underwent 120 min of MCAO following reperfusion. Immediately and 2 h after MCAO, the mice received either normal saline (sham operated and control groups) or tetrandrine (tetrandrine-treated group) intraperitoneally. Neurological defects, brain water content, and infarct volume at 24 h after stoke were used to evaluate neurological injury extent. Treatment with tetrandrine not only mitigated cerebral neurological deficits (P < 0.05) and infarct size (P < 0.01), but also decreased brian edema in the ischemic brain (P < 0.05). Then, fluorescence two-dimensional difference in gel electrophoresis was used to detect our systematic differential profiling of proteomic changes responding to tetrandrine administration. We validated that the expression of GRP78, DJ-1 and HYOU1 was associated with neuroprotective effect of tetrandrine in MCAO model by Western blotting. These findings indicate a potential neuroprotective role of tetrandrine for ischemic stroke and yield insights into cellular and molecular mechanisms of tetrandrine taking place in ischemic stroke.
缺血性脑卒中是最常见的脑卒中类型，在中国具有较高的死亡率和致残率，因此带来了巨大的疾病负担。粉防己碱是从中国草药粉防己中分离得到的一种双苄基异喹啉生物碱，已被证明具有抗炎和清除自由基的作用，甚至可以调节星形胶质细胞的激活，但粉防己碱在改善缺血性脑卒中的脑缺血/再灌注损伤中的作用尚不清楚。本研究旨在探讨粉防己碱对短暂性可逆性大脑中动脉闭塞（MCAO）诱导的小鼠脑缺血再灌注损伤的神经损伤和差异蛋白质组学变化的影响。雄性 Balb/c 小鼠分为假手术组（n=30）、MCAO+生理盐水对照组（n=30）和 MCAO+粉防己碱治疗组（n=30）。对照组和治疗组的小鼠在 MCAO 后进行 120 分钟的再灌注。MCAO 后即刻和 2 小时，小鼠分别接受生理盐水（假手术组和对照组）或粉防己碱（治疗组）腹腔注射。在中风后 24 小时，通过神经功能缺损评分、脑水含量和梗死体积评估神经损伤程度。粉防己碱治疗不仅减轻了脑的神经功能缺损（P<0.05）和梗死面积（P<0.01），还降低了缺血性脑的脑水肿（P<0.05）。然后，荧光二维差异凝胶电泳用于检测我们系统的差异蛋白质组学变化，以响应粉防己碱给药。我们通过 Western blot 验证了 GRP78、DJ-1 和 HYOU1 的表达与粉防己碱在 MCAO 模型中的神经保护作用有关。这些发现表明粉防己碱对缺血性中风具有潜在的神经保护作用，并深入了解了粉防己碱在缺血性中风中发生的细胞和分子机制。
