microRNA let-7a在刀豆蛋白A诱导的小鼠肝损伤中的作用

目的:探讨microRNA let-7a对刀豆蛋白A(Concanavalin A,ConA)小鼠肝损伤的保护作用.方法:建立ConA诱导的小鼠肝损伤模型,采用尾静脉注射let-7a慢病毒表达质粒的方法,并在造模前7d给予let-7a进行治疗干预.采用自动生化仪分析检测血清ALT变化；ELISA检测血清TNF-α、IL-6和干扰素-γ(IFN-γ)表达水平；HE染色肝脏组织病理学观察,评价let-7a治疗效果.结果:治疗组血清ALT水平较模型组明显降低(P＜0.01)；与模型组相比,治疗组IL-6水平明显降低(P＜0.01),治疗组血清炎症细胞因子TNF-α、IFN-γ水平也显著下降(P＜0.05).肝脏组织病理学检查显示,治疗组较模型组肝组织损伤程度明显减轻,炎症细胞明显减少(P＜0.01,P＜0.05).治疗组小鼠生存率明显高于模型组(P＜0.01).结论:let-7a对ConA诱导的小鼠肝损伤有保护作用,该作用可能通过抑制相关炎症细胞因子TNF-α、IL-6和IFN-γ表达来实现.

Effect of microRNA let-7a on Con A-induced hepatitis

Objective： To investigate the effects of microRNA let-7a on Con A-induced hepatitis. Methods： 24 BALB/c mice were randomly divided into model group and let-7a treatment group. The liver hepatitis models were established by the tail vein injection of Con A. Mice was infected with a lentiviral vector containing the let-7a sequence 7 days before Con A treatment. The plasma alanine transaminase （ALT） activities were measured with a 7170 Hitachi automatic analyzer. The serum TNF-α, IL-6 and IFN-γ were determined with enzyme-linked immunosorbent assay （ELISA） kits. The liver samples were fixed in 10% formalin, embedded in paraffin, sectioned and then stained with hematoxylin and eosin for histological examinations. Results： The serum ALT level was significantly decreased in the let-7a infected-mice compared to the control mice （P〈0.001）. Pretreatment with let-7a consistently reduced the extent of liver damage, as evidenced by the decreased infiltrated lymphocytes （P〈0.05） and the limited number of necrotic lesions in these mice （P〈0.01）. Furthermore, let-7a significantly improved the survival rate after Con A treatment. It was accompanied by a significant decreased level of inflammatory cytokines as TNF-α, IL-6 and IFN-γ in the serum. Conclusion： MicroRNA let-7a ameliorates Con A-induced hepatitis. It may represent as a novel therapeutic strategy in treating immune-mediated inflammatory hepatitis.