基于剂量的雷公藤抗小鼠免疫性炎症“效-毒”关联性评价

Evaluation on dosage-based efficacy-toxicity correlation of Tripterygium wilfordii against immune inflammation in mice

目的：研究雷公藤水煎液发挥抗免疫炎症药效同时产生的伴随毒性作用,为其＂药效-毒性＂相关性研究提供实验依据。方法：建立二硝基氟苯诱导小鼠迟发型超敏反应模型,连续给予不同剂量的雷公藤水煎液5 d,观察小鼠耳肿胀抑制率及其毒副作用,于末次给药后检测血中PGE2,TNF-α,IL-2,ALT,AST,PA,TBA,TBIL等生化指标水平的变化,并计算心、肝、肾、脾、肾等脏器指数。结果：连续多次给小鼠灌胃雷公藤水煎液可明显抑制DNFB致小鼠耳肿胀,其ED50及其95%可信限为0.34（0.21~0.42）g·kg-1。血中PGE2,TNF-α,IL-2含量降低,呈现一定的剂量依赖关系;小鼠血中AST,ALT,TBA,TBIL活性升高,PA含量降低。结论：雷公藤水煎液在0.59~2.34 g·kg-1具有较强的抗免疫炎症作用,呈现＂量-效＂关系,同时可对小鼠肝脏产生一定的毒副作用,高剂量（2.34~4.68 g·kg-1）可引起实质性肝损伤,肝功能指标呈现剂量依赖性。因此,雷公藤的＂功效-毒性＂具有一定的依赖于剂量的相关性,为今后临床预防药品不良反应的预警方案提供参考,确保雷公藤临床用药安全。

Objective： To study the anti-immune inflammation efficacy and toxicity of Tripterygium wilfordii decoction,in order to provide experimental basis for studies on its ″efficacy-toxicity″ correlation. Method： The delayed hypersensitivity model was established by dinitrofluorobenzene in mice. Different doses of T. wilfordii decoction was administered for 5 consecutive days. The ear swelling inhibition ratio and the toxic action were observed. After the final administration,the biochemical indexes of PGE2,TNF-α,IL-2,ALT,AST,PA,TBA,TBIL in serum were detected,and the visceral indexes of heart,liver,spleen and kidney were measured. Result： The DNFB-induced ear swelling could be notably inhibited by multiple oral administration of T. wilfordii decoction,with the ED50 and its95% confidence limit of 0. 34（ 0. 21-0. 42） g·kg-1. The contents of PGE2,TNF-α,IL-2 in serum decreased in a dose-dependent manner. The activities of serum AST,ALT,TBA,TBIL and the PA content reduced. Conclusion： T. wilfordii decoction shows a significant anti-immune inflammation efficacy within the dosage range between 0. 59 and 2. 34 g·kg-1in a dose-dependent manner. With a certain hepatotoxicity,high dose（ 2. 34-4. 68 g·kg-1） of T. wilfordii decoction can cause substantial liver injury,with a dose dependence in liver function index. Therefore,the efficacy and toxicity of T. wilfordii is dose dependent,which provides reference for preventing adverse drug reactions in clinic and developing early-warning schemes and ensure the clinical medication safety of T. wilfordii.