Zhang Wen, Song Jun-ke, Yan Rong, He Guo-rong, Zhang Xue, Zhou Qi-meng, Xiao Zhi-yong, Zhou Wen-xia, Du Guan-hua
Yao Xue Xue Bao. 2016 Nov;51(11):1717-23.
The aim of present study is to investigate the protective effects and mechanism of salvianolic acid A (SAA) on cerebral ischemia-reperfusion injury in rats. The model was established with middle cerebral artery occlusion and reperfusion (MCAO/R) with ischemia for 1.5 h and reperfusion for 24 h in adult male SD rats. After the behavior assessment, TTC assay was used to calculate the infarct volume of rat brain; the distribution of Nrf2 in nuclear and cytoplasm and expression of HO-1 were detected by Western blot. The PC12 cells injury model was established with oxygen-glucose deprivation for 6 h and reintroduction for 24 h. Cell viability was determined with MTT assay, and the expression of Nrf2 and HO-1 were detected through immunofluorescence staining. The mechanisms were investigated in PC12 cells with Nrf2 knocking down by siRNA. SAA (10 and 20 mg·kg(-1)) significantly reduced the neuronal damage in MCAO/R model, and SAA(0.5 and 5 μmol·L(-1)) increased cell viability in PC12 cells injury model. Meanwhile, the nuclear translocation of Nrf-2 and the expression of HO-1 were increased in PC12 cell and rats brain. SAA exhibited anti-cerebral ischemia- reperfusion effects. The mechanism may be related to activation of Nrf2/HO-1 signaling pathway, which promotes the synthesis and nuclear translocation of Nrf2 to enhance the expression of the antioxidant protein HO-1.
本研究旨在探讨丹酚酸A（SAA）对大鼠脑缺血再灌注损伤的保护作用及机制。采用成年雄性SD大鼠大脑中动脉闭塞再灌注（MCAO/R）法建立模型，缺血1.5小时，再灌注24小时。行为学评估后，用TTC法计算大鼠脑梗死体积；采用蛋白质免疫印迹法检测Nrf2在细胞核和细胞质中的分布及HO-1的表达。通过氧糖剥夺6小时再复氧24小时建立PC12细胞损伤模型。用MTT法测定细胞活力，通过免疫荧光染色检测Nrf2和HO-1的表达。用小干扰RNA敲低Nrf2，在PC12细胞中研究其机制。SAA（10和20mg·kg(-1)）显著减轻MCAO/R模型中的神经元损伤，SAA（0.5和5μmol·L(-1)）提高PC12细胞损伤模型中的细胞活力。同时，PC12细胞和大鼠脑中Nrf-2的核转位及HO-1的表达增加。SAA具有抗脑缺血再灌注作用。其机制可能与激活Nrf2/HO-1信号通路有关，该通路促进Nrf2的合成和核转位，增强抗氧化蛋白HO-1的表达。
