Wang Yujue, Chen Guang, Yu Xiangdong, Li Yunchao, Zhang Li, He Zongze, Zhang Nannan, Yang Xiuping, Zhao Yansheng, Li Na, Qiu Hong
Department of Neurosurgery, KaiLuan General Hospital, Tangshan, 063000, China.
Department of Neurosurgery, Tangshan People's Hospital, Tangshan, 063000, China.
Inflammation. 2016 Aug;39(4):1503-13. doi: 10.1007/s10753-016-0384-5.
Ischemic stroke can activate multiple transcription factors and cause inflammatory reactions, which involve pattern recognition receptors with immunostimulatory effects. Toll-like receptor 4 (TLR4) is one of the receptors related to innate immunity and several inflammatory reactions. The promising anti- inflammatory activity of salvianolic acid B (SAB) had been previously reported, but its effect on ischemic stroke remains unknown. An oxygen-glucose deprivation and reoxygenation (OGD/R) model in vitro and a middle cerebral artery occlusion (MCAO) model in vivo were used in this paper, and the results showned that SAB remarkably increased the viabilities of PC12 cells and primary cortical neurons after OGD/R injury and notably prevented cerebral ischemia/reperfusion (I/R) injury. SAB also significantly ameliorated NeuN release from primary cortical neurons. Further research indicated that the neuroprotection of SAB was completed through inhibiting the TLR4/MyD88/TRAF6 signaling pathway. The blocking of TLR4 by SAB also restrained NF-kB transcriptional activity and pro-inflammatory cytokine responses (IL-1β, IL-6, and TNF-α). These findings supply a new insight that will aid in clarifying the effect of SAB against cerebral I/R injury and provide the development of SAB as a potential candidate for treating ischemic stroke.
缺血性中风可激活多种转录因子并引发炎症反应，其中涉及具有免疫刺激作用的模式识别受体。Toll样受体4（TLR4）是与先天免疫和多种炎症反应相关的受体之一。此前已有报道丹酚酸B（SAB）具有良好的抗炎活性，但其对缺血性中风的影响尚不清楚。本文采用体外氧糖剥夺复氧（OGD/R）模型和体内大脑中动脉闭塞（MCAO）模型，结果表明SAB显著提高了OGD/R损伤后PC12细胞和原代皮质神经元的活力，并显著预防了脑缺血/再灌注（I/R）损伤。SAB还显著改善了原代皮质神经元中NeuN的释放。进一步研究表明，SAB的神经保护作用是通过抑制TLR4/MyD88/TRAF6信号通路实现的。SAB对TLR4的阻断也抑制了NF-κB转录活性和促炎细胞因子反应（IL-1β、IL-6和TNF-α）。这些发现提供了新的见解，有助于阐明SAB对脑I/R损伤的作用，并为将SAB开发为治疗缺血性中风的潜在候选药物提供依据。
