细胞因子在丹参酮ⅡA抗小鼠免疫性肝损伤中的作用

 目的 研究丹参酮ⅡA（tanshinoneⅡA，TSN）对小鼠免疫性肝损伤的保护作用及细胞因子在其中的作用。方法 TSN大、中、小剂量组（30、20、10 mg·kg-1）预防性给药15 d，尾静脉注射20 mg·kg-1 刀豆蛋白A(Con A)损伤小鼠肝脏。采用自动生化分析仪测定血清中天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT） 的活性；以ELISA方法测定小鼠血清中细胞因子白细胞介素（IL）-2、IL-4、IL-10、肿瘤坏死因子（TNF）-α、γ干扰素（IFN-γ）的水平，并进行肝组织病理学检查（HE染色）。结果 TSN各剂量组均能降低Con A介导的肝损伤时小鼠血清中AST、ALT的水平，以大剂量（TSN 30 mg·kg-1）最为显著，（P<0.01）;TSN各剂量组均能下调小鼠肝损伤模型组已升高的炎性细胞因子IL-2、IFN-γ、IL-4、TNF-α的含量，而上调抗炎性细胞因子IL-10的含量（P<0.05，P<0.01）。组织学检查也显示，TSN各剂量治疗组肝损伤明显低于模型组。结论 TSN对小鼠免疫性肝损伤具有保护作用，其作用机制可能与其降低淋巴细胞产生的炎性细胞因子和提高抗炎性细胞因子的作用，从而减轻T细胞毒性作用对肝细胞的损伤有关。

Role of Cytokines in Tanshinone IIA Protecting against Immune-Mediated Liver Injury in Mice Induced by Concanavalin A

OBJECTIVE To determine protective effects of tanshinone ⅡA (TSN) on immune-mdiated liver injury in mice induced by concanavalin A (Con A) and the role of cytokines in TSN protection. METHODS TSN (30, 20,10 mg·kg-1) was added into saline and given orally to the mice preteated with Con A (20 mg·kg-1) injection. After 15 d of TSN treatment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice were examined. Serum cytokines of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were determined by ELISA, and liver tissue histopathological examination (HE staining) was also used. RESULTS Histological examinations showed that the damage in livers of mice with TSN high dose treatment group was decreased compared with that of the model control group. The activities of AST and ALT of TSN treatment groups significantly decreased in the mice of Con A-mediated liver injury. TSN significantly reduced the elevated inflammatory cytokines IL-2, IL-4, IFN-γ and TNF-α levels, while increased anti-inflammatory cytokine IL-10 in the liver injury model (P<0.05, P<0.01). CONCLUSION TSN is effective on protecting immune-mediated liver injury in mice induced by Con A and the mechanism may be closely associated with downregulation of the inflammatory cytokines and upregulation of the anti-inflammatory cytokines, through which TSN reduced the toxicity of T cell-mediated liver cell damage.