Silymarin attenuated paraquat-induced cytotoxicity in macrophage by regulating Trx/TXNIP complex, inhibiting NLRP3 inflammasome activation and apoptosis
Silymarin attenuated paraquat-induced cytotoxicity in macrophage by regulating Trx/TXNIP complex, inhibiting NLRP3 inflammasome activation and apoptosis
复制标题
水飞蓟素通过调节 Trx/TXNIP 复合物、抑制 NLRP3 炎性体激活和细胞凋亡，减弱百草枯诱导的巨噬细胞细胞毒性
DOI：
10.1016/j.tiv.2017.10.017
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发表时间：
2018-02-01
影响因子：
3.2
通讯作者：
Zhao, Min
中科院分区：
文献类型：
--
作者：
Liu, Zhenning;Sun, Mingli;Zhao, Min
氧化应激和炎症参与百草枯诱导的细胞毒性。水飞蓟素可在多种病理生理过程中发挥有效的抗氧化和抗炎作用。本研究旨在探讨水飞蓟素对百草枯诱导的巨噬细胞损伤的保护作用及其可能机制。在暴露于百草枯之前，用不同剂量的水飞蓟素预处理细胞3 h。在百草枯染毒24 h后，通过MTT法和LDH释放法检测百草枯对巨噬细胞的细胞毒作用。通过测定细胞内活性氧、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）和脂质过氧化产物丙二醛（MDA）的含量来评价百草枯的氧化作用。采用免疫荧光显微镜、Western blot和Elisa检测百草枯染毒24 h后巨噬细胞NLRP 3炎性小体和细胞因子的分泌。我们的研究结果表明，百草枯可以显着引起细胞毒性和活性氧的产生，增强TXNIP的表达，并诱导NLRP 3炎性小体激活和细胞因子的分泌。水飞蓟素预处理可显著降低细胞毒性，促进Trx和抗氧化酶的表达，抑制TXNIP和NLRP 3炎性小体的活化。综上所述，水飞蓟素通过抑制氧化应激、NLRP 3炎性小体激活、细胞因子分泌和细胞凋亡来减轻百草枯诱导的巨噬细胞毒性。
Oxidative stress and inflammation are involved in paraquat-induced cytotoxicity. Silymarin can exert a potent antioxidative and anti-inflammatory effect in various pathophysiological processes. The aim of this current study is to explore the protective effect and potential mechanism of silymarin in paraquat-induced macrophage injury. Cells were pretreated with different doses of silymarin for 3 h before exposure to paraquat. At 24 h after exposure to paraquat, the paraquat-induced cytotoxicity to macrophage was measured via the MTT assay and LDH release. The levels of intracellular reactive oxygen species, GSH-Px, SOD, and lipid peroxidation product malondialdehyde were measured to evaluate the oxidative effect of paraquat. NLRP3 inflammasome and cytokines secretion in macrophage exposed to paraquat at 24 h were measured via immunofluorescence microscopy, western blot or Elisa. Our results revealed that paraquat could dramatically cause cytotoxicity and reactive oxygen species generation, enhance TXNIP expression, and induce NLRP3 inflammasome activation and cytokines secretion. The pretreatment with silymarin could remarkably reduce the cytotoxicity, promote the expression of Trx and antioxidant enzymes, and suppress the TXNIP and NLRP3 inflammasome activation. In conclusion, silymarin attenuated paraquat-induced cytotoxicity in macrophage by inhibiting oxidative stress, NLRP3 inflammasome activation, cytokines secretion and apoptosis.