益生菌抑制铁死亡减轻大鼠体外循环后肝损伤的功能及机制研究  

Probiotics attenuates cardiopulmonary bypass induced liver injury through inhibiting ferroptosis in rats

作　　者：叶玮 史辉燕 徐蕴馨 程子雯 王锐雯 李健[2] 王清秀 YE Wei;SHI Huiyan;XU Yunxin;CHENG Ziwen;WANG Ruiwen;LI Jian;WANG Qingxiu(Shanghai East Hospital of Nanjing Medical University,Shanghai 200120,China;Department of Anesthesiology,Shanghai East Hospital,School of Medicine,Tongji University,Shanghhai 200120,China)

机构地区：[1]南京医科大学上海东方临床医学院,上海200120 [2]同济大学附属东方医院麻醉科,上海200120

出　　处：《同济大学学报（医学版）》2023年第3期313-319,共7页Journal of Tongji University(Medical Science)

基　　金：上海市浦东新区卫生健康委员会重要薄弱学科项目(PWZbr2022-01)。

摘　　要：目的探讨益生菌保护体外循环后肝损伤中的功能及机制。方法将30只SD雄性大鼠随机分为4组:假手术组(Sham)、体外循环组(CPB)、体外循环+益生菌干预组(CPB+PRO)、体外循环+去铁胺组(CPB+DFO),每组5只。术后取肝组织,组织病理学检查肝损伤情况,免疫组化检测GPX4蛋白表达,化学发光法检测还原型谷胱甘肽(reduced glutathione,GSH)、丙二醛(malonaldehyde,MDA)和铁浓度,Real-time PCR检测铁死亡相关分子PTGS2(prostaglandin-endoperoxide synthase 2)、P53、GPX4(glutathione peroxidase 4)、FTH1(ferritin heavy chain1)和炎性因子IL-1β、TGF-β1、IL-4、IL-10的mRNA表达水平。结果CPB术后肝损伤明显,GPX4的蛋白和mRNA表达明显减低,GSH耗竭,MDA和铁浓度增加,PTGS2和P53 mRNA水平升高,FTH1 mRNA水平降低,炎性因子IL-1β、TGF-β1、IL-4的mRNA水平升高,IL-10 mRNA水平降低;益生菌干预组大鼠的肝损伤程度明显减轻,并明显逆转CPB诱导的上述铁死亡相关基因的表达变化及炎性因子的水平。结论益生菌可通过抑制铁死亡和抑制炎症反应,改善体外循环后的肝损伤。Objective To investigate the effect and mechanism of probiotics on the extracorporeal circulation-induced liver injury in rats.Methods Thirty male SD rats were randomly divided into 4 groups:Sham group(Sham),cardiopulmonary bypass group(CPB),probiotic group(CPB+PRO)and desferramine group(CPB+DFO).The extracorporeal circulation was performed in CPB,CPB+PRO and CPB+DFO groups;and sham operation was performed in sham group.The liver tissues were collected after the operation,and the liver injury was examined histopathologically.The GPX4 protein expression was detected by immunohistochemistry,and the concentration of glutathione(GSH),lipid oxidation(MDA)and iron were detected by chemical method.The mRNA expression levels of iron-death related molecules PTGS2,P53,GPX4,FTH1 and inflammatory factors IL-1β,TGF-β1,IL-4 and IL-10 were detected by Real-time RT-PCR.Results CPB induced liver injury,decreased the expression levels of GPX4 protein and mRNA,exhausted GSH,increased the concentration of MDA and iron,increased the expression of PTGS2 and P53,decreased the expression of FTH1,increased the levels of cytokines IL-1β,TGF-β1 and IL-4 while decreased IL-10.Upon treatment with probiotics,the degree of liver injury was significantly reduced,and the changes of iron probiotics factors and inflammatory factors induced by CPB were reversed.Conclusion Probiotics are able to attenuate the extracorporeal circulation-induced liver injury by inhibiting iron death and inflammatory response.

关 键 词：体外循环 肝损伤 铁死亡 益生菌 炎症 大鼠 

分 类 号：R619[医药卫生—外科学]