半枝莲对黄药子肝毒性的保护作用及其机制

Protection of Herba Scutellariae Barbatae against hepatotoxicity induced by Rhizoma Dioscoreae Bulbiferae and its mechanism

本文观察半枝莲醇提物(ethanol extract of Herba Scutellariae Barbatae,SE)对黄药子诱导肝毒性的保护作用及其机制。小鼠灌胃给予不同剂量SE的同时给予黄药子乙酸乙酯部位(ethyl acetate fraction of Rhizoma Dioscoreao Bulbiferae L.,EF),给药11天后,检测血清生化指标谷丙/谷草转氨酶(alanine/aspartate aminotransferase,ALT/AST)、碱性磷酸酶(alkaline phosphatase,ALP)、白蛋白(albumin,ALB)和总蛋白(total protein,TP),并进行肝脏病理切片检测。检测肝脏还原型谷胱甘肽(glutathione,GSH)含量、髓过氧化酶(myeloperoxidase,MPO)活性和血清肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白介素-6(interleukin-6,IL-6)和干扰素-γ(interferon-γ,IFN-γ)的含量。采用蛋白电泳检测血红素加氧酶(heme oxygenase-1,HO-1)、kappa B抑制剂(inhibitor of kappa B,IκB)及核因子κB(nuclear factorκB,NF-κB)p65的表达。血清生化指标检测及肝组织病理分析结果显示SE对EF连续给药诱导的肝毒性具有明显的保护作用。SE降低EF增加的肝脏MPO活性及血清TNF-α、IL-6和IFN-γ的含量,抑制EF诱导的IκB蛋白减少和NF-κB p65的磷酸化及入核。EF显著增加肝脏中GSH含量,SE能进一步升高GSH含量;同时EF组HO-1蛋白表达明显升高,而给予SE后HO-1蛋白表达降低。这些结果提示,SE可能通过抑制NF-κB信号通路缓解炎性损伤,提高机体的抗氧化能力,从而抵御EF连续给药诱导的肝损伤。

This study was conducted to test the protective activity of ethanol extract of Herba Scutellariae Barbatae（SE） against hepatotoxicity induced by Rhizoma Dioscoreae Bulbiferae in mice and its mechanism. SE was orally given to mice at various doses, and ethyl acetate fraction of Rhizoma Dioscoreae Bulbiferae（EF, 450 mg·kg-1） was also orally given at the same time. After 11 days, serum levels of alanine/aspartate aminotransferase（ALT/AST）, alkaline phosphatase（ALP）, total protein（TP） and albumin（ALB） were measured, and liver histological examination was conducted. Liver glutathione（GSH） amount, myeloperoxidase（MPO） activity and serum tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6） and interferon-γ（IFN-γ） levels were measured. The expression of heme oxygenase-1（HO-1）, inhibitor of kappa B（IκB） and nuclear factor κB（NF-κB） p65 were determined by Western blot. The results showed that SE（200 mg·kg-1） reversed EF-induced changes of serum ALT, AST, ALP, TP and ALB. Liver histology also suggests the protection of SE against EF-induced liver injury. SE reduced the increased MPO activity in liver and TNF-α, IL-6, IFN-γ contents in serum, and blocked the decrease in IκB expression and subsequent increase in phosphorylation and nuclear translocation of p65 induced by EF. EF increased liver GSH amount and heme oxygenase-1（HO-1） protein expression in mice. SE increased liver GSH amount, but decreased the expression of HO-1. All those results suggest that SE alleviates liver injury induced by consecutive administration of EF by alleviating inflammatory injury via inhibiting NF-κB signaling pathway and elevating antioxidant capacity.