Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, P.R. China.
Curr Neurovasc Res. 2014 May;11(2):107-13. doi: 10.2174/1567202611666140307124857.
Salvianolate has been reported to possess protective properties. However, its specific mechanisms have yet to be identified. Our study aimed to identify the molecular mechanism of antioxidative stress function of salvianolate on rat ischemia and reperfusion brain tissues. Rats were randomly distributed into three experimental groups: sham, model and intervention . All animal neurobehavioral tests were performed at the end of 72-h reperfusion per Longa's method, and rats with a score of 0 (no neurological deficit) or 4 (severe neurological deficit with impaired consciousness) were excluded. Brain slices were obtained after 72 h of reperfusion and stained with triphenyltetrazolium chloride. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine levels of GOLPH3, Akt/p-Akt, and mTOR/p-mTOR expressions in ischemic cortex. Salvianolate (18mg/kg intraperitoneal injection) significantly decreased the neurological deficit scores of rats in groups of 72 h I/R and reduced the number of TUNELpositive cells in the cerebral cortex when given at onset and at 24 and 48 h after reperfusion, leading to decreased cerebral infarction in rats after ischemia/reperfusion injury. Results of Western blot and qRT-PCR showed that salvianolate could significantly upregulate the expression of Golgi phosphoprotein-3 as well as the phosphorylation of Akt and mTOR. Above findings indicate that salvianolate exerts potent and long-term neuroprotective effects in the model of cerebral I/R, and Golgi phosphoprotein-3 and its downstream activation of Akt/mTOR signaling pathway may provide a new insight for the antioxidative effect of salvianolate.
丹酚酸 B 对大鼠脑缺血再灌注损伤的神经保护作用及其机制研究
丹酚酸 B 已被报道具有保护作用。然而，其具体机制尚未确定。本研究旨在探讨丹酚酸 B 对大鼠脑缺血再灌注组织抗氧化应激作用的分子机制。
假手术组、模型组和干预组。根据 Longa 评分标准，在再灌注 72 h 末对所有动物进行神经行为学测试，排除评分 0（无神经功能缺损）或 4（意识障碍严重，神经功能缺损）的大鼠。在再灌注 72 h 后获得脑切片，并用氯化三苯基四氮唑染色。采用 Western blot 分析和实时定量聚合酶链反应（qRT-PCR）检测缺血皮质中 GOLPH3、Akt/p-Akt 和 mTOR/p-mTOR 的表达水平。
丹酚酸 B（18mg/kg 腹腔注射）可显著降低 72 h I/R 大鼠的神经功能缺损评分，并减少再灌注后 24 和 48 h 时大脑皮质中 TUNEL 阳性细胞的数量，从而减少缺血再灌注损伤后大鼠的脑梗死。Western blot 和 qRT-PCR 结果表明，丹酚酸 B 可显著上调 Golgi 磷蛋白-3 的表达以及 Akt 和 mTOR 的磷酸化。
以上结果表明，丹酚酸 B 在脑缺血再灌注模型中具有强大而持久的神经保护作用，Golgi 磷蛋白-3 及其下游 Akt/mTOR 信号通路的激活可能为丹酚酸 B 的抗氧化作用提供新的见解。
