TLR4/MyD88在实验性自身免疫性肝炎小鼠中的表达和意义  

The expression and significance of TLR4 /MyD88 in mice with experimental autoimmune hepatitis

作　　者：艾国[1] 肖芳[1] 范翔雪[1] 张元亚[1] 焦云桃[1] 黄加权[1] 严伟明[1] 宁琴[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院感染科,湖北武汉430030

出　　处：《胃肠病学和肝病学杂志》2013年第8期800-803,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金面上项目(NSFC81171558)

摘　　要：目的研究Toll样受体4(Toll-like receptor4,TLR4)、髓样分化因子88(myeloid differentiation factor88,MyD88)在实验性自身免疫性肝炎(experimental autoimmune hepatitis,EAH)小鼠中的表达情况,探讨TLR4/MyD88在自身免疫性肝炎发病中的作用。方法以同种系小鼠肝组织制备的肝抗原S-100与弗氏完全佐剂等体积混合,腹腔注射免疫C57BL/6小鼠建立EAH模型,并设立正常对照组。在EAH组小鼠免疫后28d取肝组织,行石蜡包埋,病理HE染色及Masson胶原染色,免疫荧光检查血清中自身抗体,采用实时荧光定量PCR方法检测各组小鼠肝脾组织TLR4、MyD88mRNA相对表达水平,免疫组化检测肝组织中TLR4蛋白水平表达情况。结果与正常组小鼠相比,EAH小鼠肝脏中TLR4、MyD88mRNA明显升高,脾脏中TLR4、MyD88mRNA表达水平下降,肝脏中TLR4蛋白表达增加。结论 TLR4和MyD88在自身免疫性肝炎小鼠肝脏中表达水平升高,可以通过TLR4/MyD88依赖型信号途径发挥作用,并可能促进肝纤维化,在自身免疫性肝炎发生发展过程中发挥重要作用。Objective To investigate TLR4, MyD88 expression in mice with experimental autoimmune hepatitis （EAH） and determine the role of TLR4 in EAH. Methods The syngeneic liver antigen emulsified in complete Fre- und＇ s adjuvant was injected intraperitoneally into adult female C57BL/6 mice. Liver injury was assessed by liver his- topathological changes and liver fibrosis was assessed by Masson staining. The autoantibody was detected by immunofluo- rescence. The expression of TLR4, MyD88 mRNA in the mice liver and spleen were measured with real-time fluorese- cent quantitative polymerase chain reaction （Realtime-PCR）. The protein expression of TLR4 was detected by immuno- histochemistry. Results The expression of TLR4, MyD88 mRNA in liver of EAH group were significantly increased compared with normal control group （P 〈 0.05） , while there was no significant changes in spleen. Conclusion TLR4 and MyD88 which increased in liver, could run its function by MyD88-dependent pathway and promote liver fibrosis, they play important roles in the development of autoimmune hepatitis.

关 键 词：自身免疫性肝炎 髓样分化因子88 TOLL样受体4 C57BL 6 纤维化 

分 类 号：R593.2[医药卫生—内科学]