实验性自身免疫性肝炎小鼠的口服耐受诱导研究

口服耐受是一种治疗全身性炎症疾病的潜在手段。在一些动物模型中,口服自身抗原可抑制自身免疫反应。目的:观察在实验性自身免疫性肝炎(EAH)小鼠中诱导口服耐受对肝脏病变的影响。方法:在实验第1天和第7天,将新鲜制备的蛋白质浓度为0.5-2 g/L的肝抗原S-100 0.5 ml和等体积的弗氏完全佐剂(CFA)充分乳化后,予C57BL/6小鼠腹腔注射,以诱导EAH的产生。诱导:EAH前5天起,每天分别予小鼠插管喂饲1 mg和10mg的肝抗原S-100、肝抗原S-100第1峰、第2峰和第3峰,对照组以PBS 1 ml灌胃。结果:仅肝抗原S-100第1峰抗原高剂量组小鼠的肝组织学病变程度较对照组显著减轻(P<0.05),血清丙氨酸转氨酶(ALT)水平也较对照组显著下降(P<0.05)。肝抗原S-100总抗原高剂量组的血清.ALT水平较对照组显著下降(P<0.05),肝组织学病变程度呈下降趋势,但与对照组的差异无显著性。结论:口服肝抗原S-100第1峰抗原可诱导EAH小鼠的免疫耐受。

Induction of Oral Tolerance on Murine Experimental Autoimmune Hepatitis

Background: Induction of oral tolerance has been considered as a potential therapy in systemic inflammatory disease. In some animal models, Induction of oral tolerance can inhibit autoimmune reaction. Aims: To investigate the effect of oral tolerance on murine experimental autoimmune hepatitis (EAH). Methods: The EAH model was made as follows: 0.5 ml 0.5-2 g/L syngeneic hepatic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally to C57BL/6 mice at 1st and 7th day of the experiment. The mice were fed with hepatic S-100 antigen, the first, second and third fraction of hepatic S-100 antigen (1 mg and 10 mg) daily, respectively for 5 days before induction of EAH. At the same time, the controls were fed with 0.1 ml PBS. Results: The mice fed with the first fraction of hepatic S-100 antigen at high dosage showed significantly lower inflammatory activity of, the liver tissue histologically, and decrease of the level of serum alanine aminotransferase (ALT) (P< 0.05, respectively). The serum level of ALT decreased significantly in mice fed with hepatic S-100 antigen at high dosage (P<0.05), the histological severity grade of the liver was also reduced, but not reached the significant difference. Conclusions: Oral administration of the first fraction of hepatic S-100 antigen can induce immunological tolerance in EAH mice.