姜黄素通过抑制程序性坏死改善丙烯晴的神经毒性

摘要

Objective To investigate the detail protective mechanism of curcumin against neurotoxicity of acrylonitrile.Methods Cell cytotoxicity of acrylonitrile was measured by CCK-8 assay,LDH release assay and HMGB1 ELISA assay.The glutathione and ROS levels were determined by glutathione assay kit and DCF-DA.The signal pathway of necroptosis was evaluated by Western blot (WB) analysis.Results Cells treated with 1,2,4 mmol/L acrylonitrile for 24 hours significantly decreased cell viability and increased LDH,HMGB1 release.These effects were inhibited by a necroptosis inhibitor (necrostatin-1) treatment.The reduced glutathione and cell viability and increased ROS levels as well as activation of RIP-1 induced by acrylonitrile were abolished by curcumin treatment.Conclusion Curcumin improves neurotoxicity of acrylonitrile through upregulating glutathione level to inhibit necroptosis.%目的 研究姜黄素抑制丙烯晴神经细胞毒性的具体机制.方法 CCK-8、乳酸脱氢酶(LDH)检测试剂盒、ELISA试剂盒检测HMGB1释放评价丙烯晴对大脑皮层星形胶质细胞(AST)的毒性;谷胱甘肽检测试剂盒检测细胞谷胱甘肽水平、DCF-DA检测细胞活性氧水平;Western blot 法检测细胞坏死信号通路蛋白水平.结果 1,2,4 mmol/L丙烯晴处理大鼠神经AST 24 h,细胞活力显著降低、LDH和高迁移率族蛋白(HMGB1)释放显著增加,程序性坏死抑制剂necrostatin-1抑制丙烯晴诱导的细胞活力降低.姜黄素可增加丙烯晴降低的谷胱甘肽水平,抑制丙烯晴诱导的氧自由基增加及RIP-1激活,抑制丙烯晴诱导的AST活力下降.结论 姜黄素可通过上调谷胱甘肽水平抑制程序性坏死改善丙烯晴的神经毒性.