蛇菰多糖通过SLC7A11/GPX4通路减轻细胞铁死亡改善大鼠实验性肝损伤  

Polysaccharide of Balanophora involucrata Hook.f.attenuates cell ferroptosis in rats with experimental liver injury through SLC7A11/GPX4 pathway

作　　者：贾琛琛 岳蓉 曾楚华 李俸琴 唐璐 王凤杰 JIA Chen-chen;YUE Rong;ZENG Chu-hua;LI Feng-qin;TANG Lu;WANG Feng-jie(Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases(Hubei Minzu University),Enshi 445000,China;Minda Hospital of Hubei Minzu University,Enshi 445000,China;Medical School,HubeiMinzu University,Enshi 445000,China)

机构地区：[1]风湿性疾病发生与干预湖北省重点实验室(湖北民族大学),湖北恩施445000 [2]湖北民族大学附属民大医院,湖北恩施445000 [3]湖北民族大学医学部,湖北恩施445000

出　　处：《药学学报》2023年第9期2694-2699,共6页Acta Pharmaceutica Sinica

基　　金：湖北省卫生健康委员会中医药科研项目(ZY2021M033);风湿性疾病发生与干预湖北省重点实验室开放基金项目(PT022214);湖北省高校大学生创新训练项目(S202210517022)。

摘　　要：蛇菰多糖(polysaccharide of Balanophora involucrata Hook.f.,BPS)是土家民族药筒鞘蛇菰的主要活性成分之一,前期已证实具有保肝护肝作用。本研究旨在深入探讨BPS对实验性肝损伤的保护作用机制,可能与影响溶质载体家族7成员11/谷胱甘肽过氧化物酶4(solute carrier family 7 member 11/glutathione peroxidase 4,SLC7A11/GPX4)通路减轻肝细胞铁死亡有关。本实验方案经湖北民族大学实验动物伦理委员会审查,符合实验动物福利与伦理原则。实验采用一次性腹腔注射D-氨基半乳糖溶液(D-galactosamine,D-Gal N,800 mg·kg~(-1))建立急性肝损伤模型,根据前期研究给予200 mg·kg~(-1)BPS溶液灌胃干预,以铁死亡抑制剂去铁胺(desferrioxamine,DFO)为对照。结果表明,BPS干预可明显降低大鼠血清谷草转移酶(aspartate amino transferase,AST)和谷丙转移酶(alanine aminotransferase,ALT)水平,降低肝组织内活性氧(reactive oxygen species,ROS)水平和Fe~(2+)含量,降低脂质过氧化产物丙二醛(malondialdehyde,MDA)、4-羟基壬烯醛(4-hydroxynonenal,4-HNE)和脂质过氧化物(lipid peroxide,LPO)水平,提高还原型谷胱甘肽(glutathione,GSH)水平,同时减少肝内铁超载,伴肝组织内SLC7A11和GPX4蛋白表达增加,表明BPS可能通过影响SLC7A11/GPX4通路减轻肝细胞铁死亡,进而改善肝损伤。本研究为民族药筒鞘蛇菰用于辅助治疗肝损伤提供实验依据。Polysaccharide of Balanophora involucrata Hook.f.(BPS),the major component of Balanophora involucrata Hook.f.,was confirmed the protective effect on liver injury in our previous study.This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4(SLC7A11/GPX4)pathway.The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines.Rats were given intraperitoneal injection of(D-galactosamine,D-GalN)solution(800 mg·kg^(-1))one time to establish the acute liver injury model.The results showed aspartate amino transferase(AST),alanine aminotransferase(ALT)and 4-hydroxynonenal(4-HNE)levels in serum were decreased,and the contents of reactive oxygen species(ROS),Fe^(2+),malondialdehyde(MDA)and lipid peroxide(LPO)in liver tissues also decreased and glutathione(GSH)level increased after BPS administration with 200 mg·kg^(-1).Besides,BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue.In conclusion,BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway.The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.

关 键 词：筒鞘蛇菰 实验性肝损伤 溶质载体家族7成员11 谷胱甘肽过氧化物酶4 铁死亡 

分 类 号：R285.5[医药卫生—中药学]