Salvianolate lyophilized injection (SLI) strengthens blood-brain barrier function related to ERK1/2 and Akt signaling pathways
Salvianolate lyophilized injection (SLI) strengthens blood-brain barrier function related to ERK1/2 and Akt signaling pathways
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丹参多酚酸盐冻干注射液 (SLI) 增强与 ERK1/2 和 Akt 信号通路相关的血脑屏障功能
DOI：
10.1016/j.brainres.2019.06.014
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发表时间：
2019-10
期刊：
影响因子：
2.9
通讯作者：
Hu Limin
中科院分区：
文献类型：
--
作者：
Zhao Chun;Li Xueli;Li Xiaojin;Xu Yangyang;Ma Mengmeng;Wang Shaoxia;Chai Lijuan;Guo Hong;Hu Limin
丹参酚酸冻干注射液已广泛应用于急性脑梗死的治疗；然而，其增强血脑屏障（BBB）功能的分子机制尚不清楚。在这里，我们研究了SLI对bEnd血脑屏障功能的影响。3个细胞和大鼠体内一样。在氧葡萄糖剥夺/再氧化（OGD/R）损伤弯。在3个细胞中，SLI增加了上皮电阻，降低了荧光素钠通量。sli处理的细胞显示紧密连接蛋白的表达增加，包括Zonula occludens-1 （ZO-1）、Claudin-5和Occludin。此外，SLI导致ERK1/2、p38和Akt磷酸化水平降低。使用选择性抑制剂，我们发现SLI对屏障功能的积极作用在ERK1/2和Ak信号被抑制的细胞中被消除。此外，在MCAO模型大鼠中，SLI可有效减轻Evans蓝脑漏，增加脑组织ZO-1表达，抑制ERK1/2和Akt的磷酸化。综上所述，这些数据表明SLI在脑血管疾病中增强血脑屏障功能与ERK1/2和Akt信号通路相关。
The salvianolate lyophilized injection (SLI) has been widely used for the treatment of acute cerebral infarction; however, the molecular mechanism of how it strengthens blood brain barrier (BBB) function is not well understood. Here, we investigated the effects of SLI on BBB function in bEnd.3 cells as well as in rats. In oxygen glucose deprivation/reoxygenation (OGD/R)-damaged bEnd.3 cells, SLI increased transepithelial electrical resistance and decreased sodium fluorescein flux. SLI-treated cells showed increased expression of tight junction proteins, including Zonula occludens-1 (ZO-1), Claudin-5 and Occludin. Furthermore, SLI led to the decrease of phosphorylation of ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of SLI on barrier function were abolished in cells in which ERK1/2 and Ak signaling were inhibited. Moreover, in MCAO model rats, SLI effectively alleviated brain leakage of Evans blue, increased brain tissue ZO-1 expression and inhibited phosphorylation of ERK1/2 and Akt. Overall, these data suggest that SLI strengthens BBB function was interrelated ERK1/2 and Akt signaling pathways in cerebral vascular diseases.
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