丹酚酸A通过PKA/CREB/c-Fos信号通路对大鼠脑缺血再灌注损伤具有神经保护作用。
Salvianolic acid A provides neuroprotective effects on cerebral ischemia-reperfusion injury in rats via PKA/CREB/c-Fos signaling pathway.
作者信息
Yang Ran, Hu Nan, Liu Ting-Yu, Qu Yue, Liu Jie, Wang Jin-Hui, Yang Bao-Feng, Li Chun-Li
机构信息
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
出版信息
Phytomedicine. 2024 Feb;124:155326. doi: 10.1016/j.phymed.2023.155326. Epub 2023 Dec 28.
BACKGROUND
Cerebral ischemia-reperfusion injury (CIRI) is a phenomenon that pathological injury of ischemic brain tissue is further aggravated after the restoration of blood supply. The complex pathological mechanism of CIRI has led to the failure of multiple neuroprotective agents in clinical studies. Salvianolic acid A (SAA) is a neuroprotective extract from Salvia miltiorrhiza Bge., with significant pharmacological activities in the treatment of brain injury. However, the neuroprotective mechanisms of SAA remain unclear.
PURPOSE
To explore the potential protective effect of SAA on CIRI and its mechanism, and to provide experimental basis for the research of new drugs for CIRI.
STUDY DESIGN
A model of transient middle cerebral artery occlusion (tMCAO) in rats was used to simulate clinical CIRI, and the neuroprotective effect of SAA on tMCAO rats was investigated within 14 days after reperfusion. The improvement effects of SAA on cognitive impairment of tMCAO rats were investigated by behavioral tests from days 7-14. Finally, the neuroprotective mechanism of SAA was investigated on day 14.
METHODS
The neuroprotective effects and mechanism of SAA were investigated by behavioral tests, HE and TUNEL staining, RNA sequence (RNA-seq) analysis and Western blot in tMCAO rats.
RESULTS
The brain protective effects of SAA were achieved by alleviating cerebral infarction, cerebral edema, cerebral atrophy and nerve injury in tMCAO rats. Meanwhile, SAA could effectively improve the cognitive impairment and pathological damage of hippocampal tissue, and inhibit cell apoptosis in tMCAO rats. Besides, SAA could provide neuroprotective effects by up-regulating the expression of Bcl-2, inhibiting the activation of Caspase 3, and regulating PKA/CREB/c-Fos signaling pathway.
CONCLUSION
SAA can significantly improve brain injury and cognitive impairment in CIRI rats, and this neuroprotective effect may be achieved through the anti-apoptotic effect and the regulation of PKA/CREB/c-Fos signaling pathway.
背景
脑缺血再灌注损伤（CIRI）是指缺血脑组织在恢复血液供应后病理损伤进一步加重的现象。CIRI复杂的病理机制导致多种神经保护剂在临床研究中失败。丹酚酸A（SAA）是从丹参中提取的具有神经保护作用的成分，在治疗脑损伤方面具有显著的药理活性。然而，SAA的神经保护机制尚不清楚。
目的
探讨SAA对CIRI的潜在保护作用及其机制，为CIRI新药研究提供实验依据。
研究设计
采用大鼠大脑中动脉短暂闭塞（tMCAO）模型模拟临床CIRI，观察再灌注后14天内SAA对tMCAO大鼠的神经保护作用。在第7至14天通过行为学测试研究SAA对tMCAO大鼠认知障碍的改善作用。最后，在第14天研究SAA的神经保护机制。
方法
通过行为学测试、HE和TUNEL染色、RNA测序（RNA-seq）分析以及蛋白质免疫印迹法，研究SAA对tMCAO大鼠的神经保护作用及其机制。
结果
SAA通过减轻tMCAO大鼠的脑梗死、脑水肿、脑萎缩和神经损伤，发挥脑保护作用。同时，SAA可有效改善tMCAO大鼠的认知障碍和海马组织病理损伤，抑制细胞凋亡。此外，SAA可通过上调Bcl-2表达、抑制Caspase 3激活以及调节PKA/CREB/c-Fos信号通路发挥神经保护作用。
结论
SAA可显著改善CIRI大鼠的脑损伤和认知障碍，这种神经保护作用可能是通过抗凋亡作用以及调节PKA/CREB/c-Fos信号通路实现的。
Zotero 插件