细胞因子在丹参酮ⅡA抗小鼠免疫性肝损伤中的作用  

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

作　　者：覃筱燕[1] 严莉[1] 唐丽[1] 

机构地区：[1]中央民族大学生命与环境科学学院,北京100081

出　　处：《中国药学杂志》2010年第4期264-267,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30701138);中央民族大学985资助项目(cun985-3-3)

摘　　要：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。OBJECTIVE To determine protective effects of tanshinone Ⅱ A （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）, in- terleukin-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-γand 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 downregnlation of the inflammatory cytokines and upregulation of the anti-inflammatory cytokines, through which TSN reduced the toxicity of T cell-mediated liver cell damage.

关 键 词：丹参酮ⅡA 免疫性肝损伤 刀豆蛋白A 细胞因子 

分 类 号：R965[医药卫生—药理学]