目的 觀察雷公藤甲素脂質(zhì)體透皮制劑對II型膠原誘發(fā)的關(guān)節(jié)炎（CIA）的影響及不良反應(yīng)。方法 制備CIA小鼠模型。造模后小鼠隨機(jī)分為模型組、雷公藤片劑對照組、雷公藤甲素脂質(zhì)體透皮制劑（簡稱透皮制劑）高、中、低劑量（200、100、50 mg/kg）組。免疫組化法計(jì)數(shù)滑膜血管翳數(shù)目；檢測血清丙氨酸轉(zhuǎn)氨酶（ALT）和尿素氮（BUN）水平；觀察小鼠心、肝、腎、胃病理組織學(xué)改變。結(jié)果 與模型組比較，透皮制劑高劑量組和雷公藤片劑組滑膜增生血管翳數(shù)量顯著減少（P＜0.01）。與模型組比較，雷公藤片劑組小鼠血清ALT和BUN水平顯著升高（P＜0.01）；透皮制劑高、中、低劑量組小鼠血清ALT和BUN水平較雷公藤片劑組顯著降低（P＜0.01）。雷公藤片劑組小鼠顯示明顯的心、肝、腎、胃細(xì)胞及組織損傷；透皮制劑高劑量組小鼠心、肝、腎、胃均未發(fā)現(xiàn)明顯的病理改變。結(jié)論 雷公藤甲素脂質(zhì)體透皮制劑高劑量和雷公藤片劑均具有抗CIA的作用；雷公藤甲素脂質(zhì)體透皮制劑具有較高的生物活性，與口服給藥的作用相當(dāng)，且明顯減少大劑量口服給藥所產(chǎn)生的不良反應(yīng)。

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.

國家自然科學(xué)基金資助項(xiàng)目（90709041，30672590，30271562，30371787，81274147）；國家科技部重大基礎(chǔ)研究項(xiàng)目（“973”項(xiàng)目，2002CCC00300）；湖北省“十五”攻關(guān)計(jì)劃項(xiàng)目（2002AA3010C8）