抗CD200抗体对脓毒症小鼠肝脏保护作用及其机制的研究  

Protective effect of CD200 blockade in sepsis-induced liver injury in mice and its mechanism

作　　者：曹利军 苏红专 孙璐 王宜娜 李洪英 刘登辉 CAO Lijun;SU Hongzhuan;SUN Lu;WANG Yina;LI Hongying;LIU Denghui(No.906Hospital of the Chinese People's Liberation Army Joint Logistic Support Force,Ningbo 315040,Zhejiang,China)

机构地区：[1]中国人民解放军联勤保障部队第九〇六医院,宁波315040

出　　处：《现代实用医学》2021年第2期150-153,180,F0002,共6页Modern Practical Medicine

基　　金：浙江省医学会临床科研基金项目(2015ZYC-A51)。

摘　　要：目的观察CD200在脓毒症小鼠肝脏的表达情况,并进一步探讨抗CD200抗体对脓毒症小鼠肝脏的保护作用及其可能的作用机制。方法构建脓毒症小鼠模型(CLP),将C57BL/6雄性小鼠分为假手术组、脓毒症组(CLP组),每组8只,观察各组小鼠肝脏组织CD200的表达水平;将C57BL/6雄性小鼠分为假手术组,脓毒症组(CLP组)、CLP+同型对照抗体治疗组(Isotype组)、CLP+抗CD200抗体治疗组(anti-CD200组),每组8只。检测各组小鼠外周血氨基转移酶水平、肝脏病理、腹腔灌洗液细菌负荷、外周血TNF-α、IL-6的水平、肝脏组织肿瘤坏死因子-α(TNF-α)、白介素(IL)-6的mRNA水平、肝脏组织核转录因子-κB(NF-κB)磷酸化水平。结果脓毒症组小鼠的肝脏CD200表达水平明显高于假手术组(P<0.05);anti-CD200组小鼠肝脏组织的坏死程度明显轻于脓毒症组(P<0.05),TNF-α、IL-6水平低于脓毒症组(P<0.05),腹腔灌洗液细菌菌落的水平低于脓毒症组(P<0.05),NF-κB的磷酸化低于脓毒症组(P<0.05)。结论抗CD200抗体可以对脓毒症小鼠肝脏产生保护作用,其可能的机制为抑制NF-κB的磷酸化、减少炎症因子的释放。Objective To observe the expression of CD200 in sepsis-induced liver injury,and to investigate the protective effect of CD200 blockade on the liver of septic mice and its possible mechanism.Methods Sixteen C57 BL/6 male mice were randomly divided into sham operation group(Sham group)and sepsis group(CLP group),with eight in each group,and the expression level of CD200 in liver tissue of each group was observed.Then,Thirty-two C57 BL/6 male mice were randomly divided into sham operation group(Sham group),sepsis group(CLP group),CLP+isotype control antibody treatment group(Isotype group),CLP+anti-CD200 antibody treatment group(antiCD200 group),with eight in each group.The concentration of transaminase in peripheral blood,liver pathology,bacterial load of peritoneal lavage fluid,tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in peripheral blood,TNF-αand IL-6 mRNA levels in liver tissue,and neclear transcription factor-κB(NF-κB)phosphorylation level were detected.Results Compared with the Sham group,the expression of CD200 in the liver of the sepsis group was significantly increased(P<0.05).Compared with the sepsis group,the degree of necrosis in the liver tissue of mice in the anti-CD200 group was significantly reduced(P<0.05),the levels of TNF-αand IL-6 decreased(P<0.05),and the level of bacterial colonies in the peritoneal lavage fluid decreased(P<0.05),the phosphorylation level of NF-κB was down-regulated(P<0.05).Conclusions CD200 blockade can protect sepsis-induced liver injury by inhibiting NF-κB phosphorylation and reducing the release of inflammatory factors.

关 键 词：抗CD200抗体 脓毒症 肝损伤 细胞因子 核转录因子-B 

分 类 号：R-332[医药卫生]