The role of neutrophils in triptolide-induced liver injury
The role of neutrophils in triptolide-induced liver injury
复制标题
中性粒细胞在雷公藤甲素所致肝损伤中的作用
DOI：
10.1016/s1875-5364(18)30105-5
复制
发表时间：
2018-09-01
影响因子：
4.6
通讯作者：
Jiang Zhen-Zhou
中科院分区：
文献类型：
--
作者：
Wang Xin-Zhi;Zhang Shen-Ye;Jiang Zhen-Zhou
雷公藤内酯醇（TP）可引起严重的肝损伤，但其肝毒性机制尚不清楚。炎症反应可能参与了病理生理过程。中性粒细胞是无菌和非无菌炎症反应的一线免疫效应物。因此，本研究的目的是研究TP诱导的C57 BL/6小鼠肝损伤中的嗜酸性炎症反应。我们的结果表明，中性粒细胞募集和积累在肝脏，这是平行的或稍晚于肝损伤的发展。中性粒细胞诱导髓过氧化物酶的释放和CD 11b的上调，从而引起细胞毒性和肝细胞死亡。肝脏CXL 1、TNF-α、IL-6和MCP 1的表达显著增加，以调节中性粒细胞的募集和活化。Toll样受体4和9的上调也促进中性粒细胞浸润。此外，使用抗Gr 1抗体的中性粒细胞耗竭显示出对TP过量的轻度保护。这些结果表明，中性粒细胞聚集可能是继发性反应，而不是TP引起的肝损伤的原因。总之，包括中性粒细胞浸润在内的炎症反应可能在TP诱导的肝毒性中发挥作用，但可能不足以引起额外的肝损伤。
Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-alpha, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.