Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage
Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage
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水飞蓟素可防止 NLRP3 炎症小体激活并预防脑出血
DOI：
10.1016/j.biopha.2017.06.018
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发表时间：
2017
影响因子：
7.5
通讯作者：
Zhang Yan
中科院分区：
文献类型：
--
作者：
Yuan Raorao;Fan Hengyi;Cheng Shiqi;Gao WeiWei;Xu Xin;Lv Shigang;Ye Minhua;Wu Miaojing;Zhu Xingen;Zhang Yan
炎症反应介导了脑出血(ICH)的继发性损伤。在本研究中，我们测定了氧化应激和NLRP3在脑出血损伤中的参与，并分析了水飞蓟素对脑出血损伤是否具有保护作用。脑出血后24小时，氧化应激标志物(活性氧和过氧化脂质)较假手术组明显升高。脑出血后30分钟给予水飞蓟素(200 mg/kg)治疗可阻止氧化应激标志物的增加和抗氧化状态的上调。此外，脑出血后NF-κB-p65的核表达水平和促炎细胞因子的表达显著增加。脑出血后NLRP3炎性小体激活及其下游靶基因Caspase-1、IL-1β表达明显上调。水飞蓟素通过抑制NF-κB-p65水平和炎症体介导的caspase-1/IL-1β表达，显著下调炎症反应。此外，脑出血损伤后用水飞蓟素治疗可增加NRF-2/HO-1，从而改善整体细胞保护。这些发现共同表明，水飞蓟素通过阻止脑出血后炎症激活和上调NRF-2/HO-1信号转导而发挥神经保护作用。
Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24 h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200 mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status. Further, there was significant increase in nuclear levels of NF-κB-p65 and pro-inflammatory cytokine expressions post ICH injury. NLRP3 inflammasome activation and downstream targets such as caspase-1 and IL-1β expressions were significantly up regulated in ICH injury. Silymarin treatment significantly down regulated the inflammatory responses by suppressing NF-κB-p65 levels and inflammasome-mediated caspase-1/IL-1β expressions. Further, treatment with silymarin post ICH injury increased Nrf-2/HO-1 and thereby improved overall cytoprotection. These findings together show that silymarin acts as neuroprotective compound by preventing inflammatory activation and up regulating Nrf-2/HO-1 signaling post ICH injury.