复方银花解毒颗粒对干酵母诱导幼鼠发热模型的退热作用研究

Study on the Antipyretic Effect of Compound Yinhua Jiedu Granules on Dry Yeast Induced Fever in Juvenile Rats

目的:研究复方银花解毒颗粒对干酵母所致幼龄大鼠发热模型的解热作用,为复方银花解毒颗粒的儿童给药剂量提供参考。方法:将SPF级3-5周龄幼年雄性SD大鼠分为正常对照组、模型组、布洛芬组、复方银花解毒颗粒低中高三个剂量组(给药剂量分别为2.5、5、10 g·kg^-1)。各组灌胃给药,连续7天,末次给药1 h后皮下注射干酵母混悬液制备发热模型,造模后于不同时间点分别测定肛温。检测血清中IL-1β、IL-6、TNF-α含量以及下丘脑内c AMP水平。Western blot检测下丘脑炎症信号相关COX2的含量,并检测NF-κB的核转录情况,检测相关IκBα磷酸化水平变化。结果:造模后2~4 h,布洛芬、复方银花解毒颗粒高剂量组(10 g·kg^-1)均能抑制发热大鼠体温升高,在3 h时体温降低效果显著;造模3h后,与模型组比较,复方银花解毒颗粒低剂量组(2.5 g·kg^-1)能显著降低IL-6、IL-1β水平;复方银花解毒颗粒中剂量组(5 g·kg^-1)、高剂量组(10 g·kg^-1)能显著降低IL-6、TNF-α含量。复方银花解毒颗粒高剂量组(10 g·kg^-1)下丘脑内NF-κB、IκBα、COX2蛋白表达量与模型组相比也显著下降。结论:复方银花解毒颗粒能有效降低发热模型幼鼠的体温,降低体内炎症因子水平,其退热机制可能与c AMP信号转导通路和NFκB信号通路有关。

Objective: To study the antipyretic effect of Compound Yinhua Jiedu Granules on the dry yeast febrile model of juvenile rats, and to provide dosage reference of Compound Yinhua Jiedu Granules for children. Methods: The male juvenile SD rats were divided into six groups: normal control group,model group, Ibuprofen group, and Compound Yinhua Jiedu Granules low, medium and high dose groups[the doses were 2.5, 5 and 10 g·kg^-1, respectively]. Rats in each group were given the drugs by gavage according to corresponding doses for 7 days. At 1 h after the last administration, dry yeast suspensions were subcutaneously injected to prepare the heating model, and anal temperatures were measured at different time points. Levels of serum IL-1, IL-6 and TNF-α, and hypothalamus cAMP were measured. Western blot was used to detect the content of COX2 related to the inflammatory signal, the nuclear transcription of NF-κB and the phosphorylation level of IκBα in the hypothalamus. Results: After 2-4 hours of yeast injection, Ibuprofen and Compound Yinhua Jiedu Granules at highdose(10 g·kg^-1) inhibited the temperature rise of febrile rats, which was significant at 3 h. At 3 hours after yeast injection, compared with the model group, low dose of Compound Yinhua Jiedu Granules(2.5 g·kg^-1) significantly reduced the levels of IL-1 and IL-6. The contents of IL-6 and TNF-α were significantly reduced in the medium dose group(5 g·kg^-1)and the high dose group(10 g·kg^-1). Compared with the model group, the expression of hypothalamus NF-κB, IκBα and COX2 proteins in the Compound Yinhua Jiedu Granules high dose group(10 g·kg^-1) also decreased significantly. Conclusion: Compound Yinhua Jiedu Granules can effectively reduce the body temperature of the febrile juvenile rats and reduce the levels of inflammatory factors in vivo, its antipyretic mechanism may be related to the cAMP and NFκB signaling pathways.