芍药苷通过抑制NF-κB通路减轻MRL/lpr狼疮小鼠肝损伤  

Paeoniflorin ameliorates liver injury of MRL/lpr mice through inhibition of NF-κB pathway

作　　者：谢长好[1] 吴冰冰[1] 席进[2] 王锐[2] 张晨[2] 李杨磊 白善旺 张佳佳[3] 沈桐 唐笑妍 王元元[4,5] 

机构地区：[1]蚌埠医学院第一附属医院风湿免疫科,安徽蚌埠233000 [2]蚌埠医学院科研中心,安徽蚌埠233000 [3]蚌埠医学院临床医学系,安徽蚌埠233000 [4]蚌埠医学院组织学与胚胎学教研室,安徽蚌埠233000 [5]蚌埠医学院安徽省组织移植重点实验室,安徽蚌埠233000

出　　处：《细胞与分子免疫学杂志》2017年第11期1467-1471,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：安徽省自然科学基金(1608085MH215);安徽省高等学校省级自然科学研究重点项目(KJ2016A475);安徽省高等学校省级自然科学研究项目(KJ2015B009by;KJ2013B139);安徽省大学生创新项目(201610367028)

摘　　要：目的探讨芍药苷对MRL/lpr小鼠肝脏损伤的影响及其机制。方法MRL/lpr狼疮小鼠随机分为MRL/lpr组、1.5 mg/kg地塞米松处理组、20 mg/kg芍药苷处理组、40 mg/kg芍药苷处理组,每组10只;正常对照组C57 BL/6小鼠10只。微板法检测各组小鼠血清中丙氨酸氨基转移酶(ALT)与天门冬氨酸氨基转移酶(AST)含量,ELISA检测各组小鼠血清及肝脏组织中炎症因子白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)水平;HE染色检测肝组织病变情况,Western blot法检测各组小鼠肝脏受体相互作用蛋白140(RIP140)、Toll样受体4(TLR4)、磷酸化核因子κBp65(p-NF-κBp65)、核因子κBp65(NF-κBp65)、磷酸化NF-κB抑制蛋白α(p-IκBα)、IκBα蛋白的表达水平。结果与正常对照小鼠相比,MRL/lpr狼疮小鼠血清中ALT与AST含量明显增加,MRL/lpr狼疮小鼠血清及肝脏组织中炎症因子IL-1β、IL-6、TNF-α的表达量显著增加。肝组织中有炎症细胞浸润,MRL/lpr狼疮小鼠肝脏组织中RIP140、TLR4、NF-κB蛋白水平显著增加。芍药苷和地塞米松一样能显著降低MRL/lpr狼疮小鼠血清中ALT和AST含量,减少MRL/lpr狼疮小鼠血清及肝脏组织中IL-1β、IL-6、TNF-α水平,减轻肝组织炎细胞浸润;并能显著降低MRL/lpr狼疮小鼠肝组织中RIP140、TLR4、p-NF-κBp65、NF-κBp65蛋白水平。结论芍药苷通过抑制NF-κB信号通路,从而对MRL/lpr狼疮小鼠肝脏损伤起到保护作用。Objective To investigate the effects of paeoniflorin（PF） on liver injury of MRL/lpr mice and its underlying mechanisms. Methods The research included 10 normal control C57 BL/6 mice and 40 MRL/lpr mice. MRL/lpr mice were randomly assigned equally to a blank control group,a dexamethasone（ 1. 5 mg/kg） group,and two PF（ 20,40 mg/kg）groups. The serum levels of alanine transaminase（ ALT） and aspartate transaminase（ AST） were tested with microplate assay. Inflammatory cytokines in the serum and liver were also detected using ELISA. Liver pathological changes were observed using HE staining. The protein levels of receptor interacting protein140（ RIP140）,Toll-like receptor 4（ TLR4）,p-NF-κBp65,NF-κBp65,p-IκBα and IκBα in the liver were detected by Western blot analysis. Results PF significantly decreased the serum levels of AST and ALT,obviously decreased the expressions of the inflammatory cytokines IL-1 β,IL-6 and TNF-α in the serum and liver,alleviated liver pathological changes and inhibited the expressions of RIP140,TLR4,p-NF-κBp65,p-IκBα proteins in the MRL/lpr mice. Conclusion PF has protective effects against liver injury in MRL/lpr mice by inhibiting NF-κB pathway.

关 键 词：系统性红斑狼疮 芍药苷 肝脏 炎症 

分 类 号：R593.24[医药卫生—内科学]