目的 研究雷公藤多苷片发挥抗炎作用剂量下伴随的肝毒性作用，为其“药效-毒性”相关性研究提供实验依据。方法 取昆明种小鼠50只，随机分为5组，即正常对照组，雷公藤多苷片高、中、低剂量组（54.6，27.3，13.7 mg·kg-1），美洛昔康片组（3.9 mg·kg-1），每组10只。以巴豆油混合致炎液建立小鼠耳肿胀模型，计算小鼠的耳肿胀度和肿胀抑制率，末次给药后检测血清中前列腺素E2（PGE2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、前白蛋白（PA）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆汁酸（TBA）和总胆红素（TBIL）等生化指标含量和活性的变化，并计算心、肝、脾、肾等脏器指数，进行肝组织病理学检查。结果 雷公藤多苷片在13.7~54.6 mg·kg-1范围内，可明显抑制巴豆油混合致炎液致小鼠耳肿胀，小鼠血清中PGE2、TNF-α和IL-2含量降低，血清ALT、AST、TBA、TBIL活性升高，PA含量降低，肝指数变大。组织病理学检查显示，雷公藤多苷片可引起肝细胞水肿和浸润。结论 雷公藤多苷片在13.7~54.6 mg·kg-1范围内既有明显的药效作用，又有一定的肝损伤作用，均呈现明显的“量—效—毒”关系，其抗炎机制与减少PGE2炎性介质和血TNF-α、IL-2的产生和释放有关。

Objective The hepatotoxicity of Tripterygium wilfordii glycosides（TWG） in the anti-inflammation dosage was researched to provide experimental basis for the correlation of efficacy- toxicity. Methods Fifty Kunming mice were evenly randomized into 5 groups，namely normal control group，meloxicam group（3.9 mg·kg-1），and high-，medium- and low-dose TWG groups（54.6，27.3，13.7 mg·kg-1）. The model of mice ear edema was established with the mixture of compound croton oil and inflammation-induced agent. After gastric gavage for 3 consecutive days，the effects of TWP on the ear edema and the edema-inhibition ratio were observed. After the last medication，the serum contents and activities of prostaglandin E2（PGE2），tumor necrosis factor alpha（TNF-α），interleukin-2（IL-2），alanine aminotransferase（ALT），aspartate aminotransferase（AST），pre-albumin（PA），total bile acid（TBA），and total bilirubin（TBIL） were detected，the indexes of heart，liver，spleen and kidney were measured，and the hepatic histopathological features were observed. Results TWG in the dosage of 13.7~54.6 mg·kg-1 showed an obvious inhibition of mice ear edema induced by the mixture of croton oil and inflammation-induced agent，decreased the serum contents of PGE2，TNF-α and IL-2，increased the activities of serum ALT，AST，TBA，TBIL and liver index， and reduced the content of PA. The results of pathological examination showed that TWG could cause the edema and infiltration liver cells. Conclusion TWG in the dosage range of 13.7~54.6 mg·kg-1 exerts obvious pharmacological actions but also induce certain liver injury，showing markedly dosage-efficacy-toxicity correlation. The mechanism of its anti-inflammatory effect is probably related to the decrease of generation and release of inflammatory factors such as PGE2，TNF-α and IL-2.

R285.5

国家重点基础研究发展计划（973）中医基础理论专项资助项目课题（2009CB522802）。