目的 观察雷公藤甲素脂质体透皮制剂对II型胶原诱发的关节炎（CIA）的影响及不良反应。方法 制备CIA小鼠模型。造模后小鼠随机分为模型组、雷公藤片剂对照组、雷公藤甲素脂质体透皮制剂（简称透皮制剂）高、中、低剂量（200、100、50 mg/kg）组。免疫组化法计数滑膜血管翳数目；检测血清丙氨酸转氨酶（ALT）和尿素氮（BUN）水平；观察小鼠心、肝、肾、胃病理组织学改变。结果 与模型组比较，透皮制剂高剂量组和雷公藤片剂组滑膜增生血管翳数量显著减少（P＜0.01）。与模型组比较，雷公藤片剂组小鼠血清ALT和BUN水平显著升高（P＜0.01）；透皮制剂高、中、低剂量组小鼠血清ALT和BUN水平较雷公藤片剂组显著降低（P＜0.01）。雷公藤片剂组小鼠显示明显的心、肝、肾、胃细胞及组织损伤；透皮制剂高剂量组小鼠心、肝、肾、胃均未发现明显的病理改变。结论 雷公藤甲素脂质体透皮制剂高剂量和雷公藤片剂均具有抗CIA的作用；雷公藤甲素脂质体透皮制剂具有较高的生物活性，与口服给药的作用相当，且明显减少大剂量口服给药所产生的不良反应。

Abstract: Objective To observe the effects and side effects of transdermal liposome preparation of triptolide (TLPT) on collagen II-induced arthritis (CIA). Methods The model of mice with CIA was established. And then the mice were randomly divided into model, Tripterygium wilfordii Tablet (TWT), TLPT high-, mid-, and low-dose (200, 100, and 50 mg/kg) groups. Immuno- histochemical method was used to count the number of pannus in knee join; ALT and BUN levels were measured. Pathological changes of heart, liver, kidney, and stomach were observed by histologic method. Results Compared with the model group, the number of pannus in knee join in TLPT high-dose group and TWT group was significantly reduced (P < 0.01). The ALT and BUN levels in mice serum of TWT group were obviously increased (P < 0.01). The ALT and BUN levels in serum of mice in TLPT high-, mid-, and low-dose groups were significantly reduced (P < 0.01). The cell and tissue damage were obvious in TWT group, but no obviously pathological changes were observed in TLPT high-dose group. Conclusion The TLPT high-dose group and the TWT group could protect against CIA in mice. The biological activities of TLPT are higher and equivalent to ig administration, but the side effects of ig TLPT administration in high-dose are decreased largely.

国家自然科学基金资助项目（90709041，30672590，30271562，30371787，81274147）；国家科技部重大基础研究项目（“973”项目，2002CCC00300）；湖北省“十五”攻关计划项目（2002AA3010C8）