不同药对配伍对栀子引起的肝损伤的保护作用研究

Protective effect of different formula compatibilities on Fructus Gardeniae-induced hepatotoxicity

目的探讨不同药对配伍对栀子引起的大鼠肝损伤的保护作用。方法大鼠随机分为正常对照组、栀子组(1.17 g·kg^(-1))、栀子+大黄组(栀子-大黄=3∶8)、栀子+黄连组(栀子-黄连=1∶1)、栀子+黄芩组(栀子-黄芩=1∶1)。按照上述配比,各组大鼠每日灌胃给予相应药物1次,连续进行7 d。给药结束后检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6(IL-6)、IL-1β水平;计算脏器系数;HE染色检测肝组织病理变化;检测超氧化物歧化酶(SOD)活性,还原型谷胱甘肽(GSH)、丙二醛(MDA)及铁含量;Western blot检测肝组织谷胱甘肽过氧化物酶4(GPX4)、血红素氧合酶(HO-1)、溶质载体家族7成员11(SLC7A11)蛋白的表达;qRT-PCR检测GPX4和SLC7A11 mRNA的水平。结果与正常对照组比,栀子组血清ALT、AST、ALP、LDH、TNF-α、IL-6、IL-1β水平明显上升;肝脏系数显著上升,胸腺系数明显下降;病理切片检测发现明显的肝细胞坏死及炎性细胞浸润;GSH和SOD水平显著下降;MDA和铁含量显著升高。GPX4和SLC7A11的蛋白及mRNA表达降低,HO-1蛋白表达增加。与大黄、黄连、黄芩配伍后,ALT、AST、ALP、LDH、TNF-α、IL-6、IL-1β水平及肝脏系数明显降低,肝组织病理得到改善;GSH和SOD水平明显提升;MDA和铁含量减少。GPX4、SLC7A11的蛋白和mRNA及HO-1的蛋白表达水平升高。结论大黄、黄连、黄芩与栀子药对配伍可有效减轻栀子肝脏毒性,其作用机制与抑制氧化应激和铁死亡有关。

Objective To determine the protective effect of different formula compatibilities with Rhubarb,Rhizoma Coptidis or Scutellaria Baicalensis on Fructus Gardeniae-induced hepatotoxicity.Methods SD rats were randomly divided into a normal control,a Fructus Gardeniae(1.17 g·kg^(-1)),a Fructus Gardeniae plus Rhubarb(3∶8),a Gardeniae plus Rhizoma Coptidis(1∶1),and a Gardeniae plus Scutellaria Baicalensis(1∶1)group.The rats were administrated with the above drugs by gavage once daily for 7 days.After the administration,the activities of serum ALT,AST,ALP,LDH,TNF-α,IL-6,and IL-1βwere detected.The organ coefficient was calculated.The pathological changes in the liver tissues were evaluated by HE staining.The SOD activity,GSH,MDA,and iron levels were assessed.The protein levels of GPX4,SLC7A11,and HO-1 were determined by Western blot.The mRNA levels of GPX4 and SLC7A11 were evaluated by qRT-PCR.Results Compared with the control group,the serum levels of ALT,AST,ALP,LDH,TNF-α,IL-6,and IL-1β,and the liver coefficient was increased in Frutus Gardeniae group,while the thymus coefficient were reduced.We also observed obvious necrosis of liver cells and inflammatory cell infiltration in the liver tissues.The levels of GSH and SOD were declined,but MDA and iron rose raised in the Fructus Gardeniae group.The protein and mRNA expression of GPX4 and SLC7A11 was declined and HO-1 expression was elevated in the Fructus Gardeniae group.After compatibility with Rhubarb,Rhizoma Coptidis or Scutellaria Baicalensis,the above changes induced by Fructus Gardeniae were partly reversed.Conclusion Compatibility with Rhubarb,Rhizoma Coptidis or Scutellaria Baicalensis effectively attenuates Fructus Gardeniae-induced hepatotoxicity via repressing the oxidative stress and ferroptosis.