他克莫司减少瘙痒的机制研究_他克莫司机制

欧洲药理学杂志---他克莫司减少瘙痒的机制研究 2009年10月22日03:13 来源：好医生网站

Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus.

Inagaki N, Shiraishi N, Igeta K, Nagao M, Kim JF, Chikumoto T, Itoh T, Katoh

H , Tanaka H, Nagai H.

Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502-8585, Japan. 发表在最新一期欧洲药理学杂志上的题为《Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus. 》的文章从药物机制上深入探讨了他克莫司减少皮肤瘙痒的机制，发现对激素无效的顽固性瘙痒他克莫司仍能很大程度的缓解症状。他克莫司的这一作用有可能与其减少P 物质有很大的关系。这为该药的临床使用又一次提供了有力的作用机制依据。 Itching is the most important problem in atopic dermatitis and tacrolimus has been suggested to attenuate the itching by topical application. However, the anti-itch mechanism of tacrolimus has not been well elucidated. In the present study, an allergic dermatitis accompanied by frequent scratching behaviors was induced by repeated paintings with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse ear and the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior were comparatively examined. Repeated DNFB paintings caused a typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behaviors. Both tacrolimus and dexamethasone given topically for 10days before the final challenge significantly inhibited the ear swelling and reduced the expression of interferon-gamma mRNA. Dexamethasone inhibited the accumulation of eosinophils completely, although tacrolimus did not. Both drugs did not affect the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior, whereas dexamethasone failed to affect it. Repeated DNFB challenge depleted substance P in the dermis. Treatment with tacrolimus before the final challenge completely inhibited the recovery of substance P content, whereas dexamethasone facilitated the recovery. DNFB-induced ear swelling and scratching behavior were significantly inhibited by FK888, a tachykinin NK(1) receptor antagonist. Therefore, substance P seems to participate in the induction of ear swelling and scratching behavior upon final challenge with DNFB, and depletion of substance P by tacrolimus in the dermis contributes to its inhibition of ear swelling and scratching

behavior at least in part.

Eur J Pharmacol. 2009 Oct 8