PKCδ在丹酚酸B抗对乙酰氨基酚肝损伤中的作用研究

PKCδrelated signal pathway involves in protective effects of salvianolic acid B against acetaminophen induced hepatotoxicity

目的:探讨PKCδ在丹酚酸B(SalB)抗对乙酰氨基酚(APAP)肝损伤中的作用。方法:通过MTT法、细胞内还原型GSH含量测定、细胞LDH溢出量测定检测SalB抗APAP肝损伤作用。Western Blot法检测SalB对Nrf2核移位的影响。应用PKCδ抑制剂或siRNA干扰技术,探索PKCδ在SalB抗APAP肝损伤中的作用,Western Blot法检测PKCδ表达及Nrf2激活。结果:SalB可明显减轻APAP造成的HepG2细胞损伤,同时激活PKCδ,促进Nrf2核移位。PKCδ选择性阻断剂Rottlerin可减弱以上保护作用。PKCδ敲除明显减弱SalB对Nrf2核移位的诱导作用。结论:SalB可减轻APAP所致肝细胞损伤,其机制与SalB通过PKCδ激活Nrf2通路有关。

OBJECTIVE To explore potential roles of PKCδin protective effects afforded by salvianolic acid B（SalB）against acetaminophen（APAP）induced acute liver injury.METHODS Protective effects of SalB against APAP-induced cell damage were characterized by measuring cell viability,GSH content and LDH level.Activation of Nrf2 by SalB was determined by Western-blot.To further explore roles of PKCδinvolved,cells were treated with specific inhibitor or siRNA of PKCδ.Then expression of PKCδand activation of Nrf2 were tested by Western-blot.RESULTS SalB ameliorated APAP-induced acute liver injury,which was correlated with Nrf2 translocation and PKCδactivation.Rottlerin,a specific inhibitor of PKCδ,markedly reduced protective effects afforded by SalB.In addition,PKCδknock down significantly abolished activation of Nrf2 induced by SalB.CONCLUSION SalB protects against APAP-induced liver injury via activation of PKCδ/Nrf2 pathways.