牛磺酸通过调控AKT/NF-κB通路改善脓毒症小鼠肝脏损伤的保护作用  

Protective effect of taurine against LPS-induced liver injury in septic mice based on AKT/NF-κB pathway

作　　者：胡玉莲[1] 安佰丽[1] 刘超[2] 高慧婕[2] Hu Yulian;An Baili;Liu Chao;Gao Huijie(Rizhao People's Hospital,Rizhao 276826,China;College of Pharmacy,Jining Medical University,Rizhao 276826,China)

机构地区：[1]日照市人民医院,日照276826 [2]济宁医学院药学院,日照276826

出　　处：《国际医药卫生导报》2023年第19期2782-2788,共7页International Medicine and Health Guidance News

基　　金：山东省中医药科技项目(Z-2022034);济宁市重点研发计划项目(2022YXNS159);2021年教育部产学合作协同育人项目(202101010010)。

摘　　要：目的探究牛磺酸对脂多糖(LPS)所致脓毒症小鼠肝损伤的保护作用。方法本研究于2022年2月至7月进行。50只ICR小鼠(4~5周龄,体质量18~22 g)分为空白对照组(Control组)、LPS造模组(LPS组)、牛磺酸低剂量组(L+L组,100 mg/kg)、牛磺酸中剂量组(L+M组,200 mg/kg)和牛磺酸高剂量组(L+H组,400 mg/kg),牛磺酸连续腹腔注射给药7 d,实验第7天腹腔注射LPS建立脓毒症模型。测定小鼠肝脏、肾脏和肺脏指数;外周血血常规分析;测定肝脏丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力;酶联免疫吸附试验(ELISA)检测血清白细胞介素(IL)-1β、IL-6和IL-10的含量;Western blot及免疫组化检测肝脏核因子(NF)-κB、核因子κB抑制蛋白(IκB)和蛋白激酶B(AKT)的表达变化。采用t检验或单因素方差分析。结果与LPS组相比较,牛磺酸用药组的肝脏、肾脏及肺脏指数均明显降低(P<0.05,P<0.01,P<0.001);血常规显示白细胞计数和粒细胞比率明显降低,淋巴细胞比率明显升高(P<0.05,P<0.001);肝脏组织内SOD活力明显升高且MDA含量显著降低(P<0.05,P<0.01);血清IL-1β和IL-6明显降低,IL-10明显升高(P<0.05,P<0.01,P<0.001)。与Control组相比,LPS组肝脏组织内NF-κB、AKT蛋白表达上升,IκB蛋白表达降低;与LPS组相比,L+H组NF-κB、AKT蛋白表达下降,IκB蛋白表达升高。结论牛磺酸可降低脓毒症小鼠体内炎症因子的水平,增强肝脏抗氧化能力,缓解LPS所致肝脏损伤,可能通过抑制肝脏AKT/NF-κB通路发挥抗炎活性。本实验为牛磺酸作为有效抗炎、抗氧化药物应用于脓毒血症的临床治疗提供科学的实验依据。Objective To investigate the anti-inflammatory and antioxidant effects of taurine on liver injury induced by lipopolysaccharide(LPS)in septic mice and elucidate the underlying mechanisms.Methods The study was conducted from February to July 2022.Fifty ICR mice(4-5 weeks old,body weight 18-22 g)were randomly divided into five groups:control group,LPS group,and taurine-treated groups with low,mid,and high doses(100,200,and 400 mg/kg).Taurine was injected intraperitoneally for 7 days,and LPS was injected intraperitoneally on the 7th day to establish the sepsis model.The indices of liver,kidney,and lung were measured.Blood routine analysis was conducted.The content of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)in the liver were determined.Serum concentrations of interleukin(IL)-1β,IL-6,and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of nuclear factor(NF)-κB,nuclear factorκB inhibitory protein(IκB),and protein kinase B(AKT)in the liver were detected by Western blot and immunohistochemistry(IHC).t test or one-way analysis of variance were used.Results The taurine-treated groups exhibited significantly lower indices of liver,kidney,and lung compared with the LPS group(P<0.05,P<0.01,P<0.001).Blood routine analysis demonstrated significantly lower white blood cell count and granulocyte ratio and significantly higher lymphocyte ratio in the taurine-treated groups compared with the LPS group(P<0.05,P<0.001).The taurine-treated groups had significantly higher SOD activity and significantly lower MDA content compared with the LPS group(P<0.05,P<0.01).Moreover,ELISA results showed significantly lower levels of IL-1βand IL-6 and significantly higher level of IL-10 in the taurine-treated groups compared with the LPS group(P<0.05,P<0.01,P<0.001).Compared with the control group,the protein expressions of NF-κB and AKT increased and the protein expression of IκB decreased in the liver tissues of the LPS group.Compared with the LPS group,the protein expressions of NF-κB a

关 键 词：牛磺酸 脂多糖 AKT NF-κB IΚB 动物实验 

分 类 号：R459.7[医药卫生—急诊医学]