目的 考察热毒宁注射液对内生致热原性发热家兔的解热作用及其机制研究。方法 48只家兔随机分为6组,每组8只,分别为对照组、模型组、安乃近注射液(0.024 g/kg)组和热毒宁注射液(1.02、2.04、5.08 g/kg)组。对照组、模型组给予等量生理盐水,给药容积5 mL/kg。除对照组耳缘iv生理盐水外,其他各组给药0.5 h后耳缘iv内生致热原(1.5 mL/kg)。测定家兔注射内生致热原后4 h内体温,记录平均体温的变化(ΔT)。发热1 h后测定家兔血清中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平以及脑脊液、下丘脑中环磷酸腺苷(cAMP)。结果 热毒宁注射液5.08、2.04 g/kg组与模型组比较,各时间点的ΔT明显降低,差异具有统计学意义(P< 0.05、0.01)。热毒宁注射液1.02、2.04、5.08 g/kg组下丘脑、脑脊液中cAMP水平及血清IL-1β、TNF-α水平与模型组比较明显减少(P< 0.05)。结论 热毒宁注射液对家兔内生致热原性发热有显著的解热作用,通过减少血清中IL-1β、TNF-α水平,降低脑脊液和下丘脑中cAMP含量来发挥解热作用。

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.

国家科技部重大新药创制项目(2013ZX09402203)