目的 考察熱毒寧注射液對內(nèi)生致熱原性發(fā)熱家兔的解熱作用及其機制研究。方法 48只家兔隨機分為6組,每組8只,分別為對照組、模型組、安乃近注射液(0.024 g/kg)組和熱毒寧注射液(1.02、2.04、5.08 g/kg)組。對照組、模型組給予等量生理鹽水,給藥容積5 mL/kg。除對照組耳緣iv生理鹽水外,其他各組給藥0.5 h后耳緣iv內(nèi)生致熱原(1.5 mL/kg)。測定家兔注射內(nèi)生致熱原后4 h內(nèi)體溫,記錄平均體溫的變化(ΔT)。發(fā)熱1 h后測定家兔血清中白細(xì)胞介素-1β(IL-1β)、腫瘤壞死因子-α(TNF-α)水平以及腦脊液、下丘腦中環(huán)磷酸腺苷(cAMP)。結(jié)果 熱毒寧注射液5.08、2.04 g/kg組與模型組比較,各時間點的ΔT明顯降低,差異具有統(tǒng)計學(xué)意義(P< 0.05、0.01)。熱毒寧注射液1.02、2.04、5.08 g/kg組下丘腦、腦脊液中cAMP水平及血清IL-1β、TNF-α水平與模型組比較明顯減少(P< 0.05)。結(jié)論 熱毒寧注射液對家兔內(nèi)生致熱原性發(fā)熱有顯著的解熱作用,通過減少血清中IL-1β、TNF-α水平,降低腦脊液和下丘腦中cAMP含量來發(fā)揮解熱作用。

Objective To investigate the antipyretic effects of Reduning Injection on rabbits with fever induced by endogenous pyrogen and its mechanism. Methods Forty-eight rabbits were divided randomly into six groups, and each group had eight animals. They were control group, model group, Analgin Injection (0.024 g/kg) group, and Reduning Injection (1.02, 2.04, and 5.08 g/kg) groups. All rabbits were administered solution with volumes of 5 mL/kg, and ear iv endogenous pyrogen (1.5 mL/kg) at 0.5 h after administration except control group with normal saline. Body temperature changes of rabbit with fever induced by endogenous pyrogen during 4 h were observed and recorded. Levels of IL-1β and TNF-α in serum and cAMP in the hypothalamus and cerebrospinal fluid were measured after fever for 1 h. Results Body temperature of fever rabbits were reduced significantly in Reduning injection groups, as well as the levels of cAMP in the hypothalamus and cerebrospinal fluid, IL-1 β/TNF-α in serum. Compared with model group, body temperature changes of rabbit in Reduning Injection (5.08 and 2.04 g/kg) groups were significantly decreased, with significant difference between two groups (P < 0.05, 0.01). The levels of IL-1β, TNF-α in serum and cAMP in the hypothalamus and cerebrospinal fluid in Reduning Injection (1.02, 2.04, and 5.08 g/kg) groups were obviously reduced (P < 0.05). Conclusion Reduning Injection has obvious antipyretic effects on rabbits with fever induced by endogenous pyrogen, and it can reduce the levels of IL-1β and TNF-α in the serum, and decrease the contents of cAMP in the hypothalamus and cerebrospinal fluid.

國家科技部重大新藥創(chuàng)制項目(2013ZX09402203)