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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 study the protective effect of tanshinone Ⅱ A (TSN) on immunological liver injury in mice and the role of cytokines in it. Methods The TSN groups (30, 20 and 10 mg.kg-1) were given prophylactically for 15 days and the mice were challenged with 20 mg.kg-1 concanavalin A (Con A) through the tail vein. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were measured by automatic biochemical analyzer. The levels of cytokines interleukin (IL) -2, IL-4, IL-10, tumor necrosis factor (TNF) -α, interferon-γ (IFN-γ) were detected. Liver histopathology was also performed. Results The levels of AST and ALT in serum of mice with Con A-mediated liver injury were significantly lower than those of TSN group (TSN 30 mg.kg-1, P <0.01) Group can down-regulate the levels of inflammatory cytokines IL-2, IFN-γ, IL-4 and TNF-α in model mice with liver injury and up-regulate the content of anti-inflammatory cytokines IL- <0.05, P <0.01). Histological examination also showed that each dose of TSN treatment group liver injury was significantly lower than the model group. Conclusion TSN can protect mice from immunological liver injury. Its mechanism may be related to the decrease of inflammatory cytokines produced by lymphocytes and the enhancement of anti-inflammatory cytokines, so as to reduce the T cell cytotoxicity on liver cells.