目的:探讨可溶性纤维介素蛋白2(solublefgl2,sfgl2)在小鼠自身免疫性肝炎中的作用。方法:将s-100肝抗原与弗氏完全佐剂经腹腔注入到C57BL/6小鼠体内。通过肝脏病理改变和血清ALT和AST水平观察肝脏的损伤程度。用免疫组织化学方法检测肝脏和脾脏组织中纤维素介素蛋白2(龟12)的表达;免疫印迹方法检测脾脏混合淋巴细胞培养的上清液和细胞中fgl2的表达;免疫组化双染检测小鼠肝脏中培12与纤维蛋白的表达,肝脏连续切片中用免疫组化法分别检测fgl2与纤维蛋白的表达。结果:AIJT和AST明显升高,肝脏组织中可见大量炎性细胞浸润和坏死形成。免疫组化观测模型组肝脏非实质细胞和脾脏中有fgl2的明显高表达。Western—blot方法发现脾脏淋巴细胞培养的上清液中有fgl2的表达,而沉淀的细胞则没有;免疫组化双染观测到fgl2与纤维蛋白的沉积无关,在连续切片同一部位中,只有fgl2的表达而没有纤维蛋白的表达。结论:sfgl2是由脾脏的T淋巴细胞所分泌的,在肝抗原诱导的自身免疫性肝炎小鼠模型中发挥了重要的作用。
Objective: To investigate the role of fibrinogen-like protein 2 (fgl2) in murine experimental autoimmune hepatitis (EAH) development. Methods: To induce murine EAH, the syngeneic S-100 antigen emulsified in complete Freund's adjuvant was injected intraperitoneally into adult male C57BL/6 mice. Liver injury was assessed by liver history and serum ALT and AST levels. The expression of fgl2 in livers and spleens of mice was examined by immunohistochemistry staining. The level of serum ALT and expression of fgl2 were measured. To detect whether menlbrane fgl2 or soluble fgl2 plays an important role in autoimmune hepatitis (AIH), it was examined by Western-blot and dual immunohistochemical staining. Results: In murine models, infiltration of inflammatory cells and foci of necrosis were observed in liver tissues. By immunohistochemistry staining, fgl2 was highly expressed in nonparenchymal cells of liver and spleen tissues in mice with EAH whereas with little or no expression in control mice. Sfgl2 could be expressed and secreted by splenic T-lymphocytes in mice of EAH, but not in normal mice. Conclusion: Soluble fgl2 plays a vital role in an animal model of AIH induced by liver antigen. These results suggested that the sfgl2 expressed by splenic T lymphocytes might be involved in the pathogenesis and development of EAH. These data provide the first evidence to demonstrate that sfgl2 exert effects on EAH by T cells.