清火胶囊对发热大鼠的解热作用及其机制研究

Antipyretic Effect and Mechanism of Qinghuo Capsules on Lipopolysaccharide-induced Fever in Rats

目的:探究清火胶囊对脂多糖所致大鼠发热模型的解热作用,并研究其作用机制。方法:60只SPF级SD健康大鼠按基础体温随机分为6组:正常对照组、模型组、阳性对照组(阿司匹林,0.125 g·kg^(-1))、清火胶囊高(1 g·kg^(-1))、中(0.5 g·kg^(-1))、低(0.25 g·kg^(-1))剂量组,每组10只。连续给药7 d,末次给药30 min后给予20μg·kg^(-1)脂多糖溶液造模,记录造模后4 h内的大鼠体温变化,取大鼠血清测定血清白细胞介素⁃6(IL⁃6)、白细胞介素⁃1β(IL⁃1β)、肿瘤坏死因子⁃α(TNF⁃α)含量,取大鼠下丘脑测定环磷酸腺苷(cAMP)、下丘脑前列腺素E_(2)(PGE_(2))以及下丘脑腹中隔区精氨酸加压素(AVP)水平。结果:造模后,清火胶囊高、中剂量组在造模后3、4 h的体温升高幅度低于模型组,低剂量组在4 h的体温升高幅度低于模型组(P<0.05);清火胶囊高剂量组TNF⁃α、IL⁃6、IL⁃1β水平均低于模型组,清火胶囊中剂量组TNF⁃α、IL⁃1β水平均低于模型组,清火胶囊低剂量组TNF⁃α水平均低于模型组(P<0.05)。清火胶囊各剂量组大鼠cAMP、PGE2水平均低于模型组(P<0.05),AVP水平与模型组比较差异无统计学意义(P>0.05)。结论:清火胶囊能够降低发热大鼠体温,抗炎效果明显,其解热功效可能与降低各种炎症因子水平,抑制下丘脑发热介质PGE2与cAMP有关。

Objective:To explore the antipyretic effect of Qinghuo capsules on lipopolysaccharide induced fever in rats and its action mechanism.Methods:Sixty SPF SD healthy rats were randomly divided into six groups according to the basal body temperature:normal control group,model group,positive control group(aspirin,0.125 g·kg^(-1)),and high(1 g·kg^(-1)),medium(0.5 g·kg^(-1))and low(0.25 g·kg^(-1))dosage groups of Qinghuo capsules with 10 rats in each group.The treatment course was 7 days,and 20μg·kg^(-1) lipopolysaccharide solution was given 30 minutes after the last drug administration to make fever model.The changes of body temperature within 4 hours after modeling were observed,and the serum levels of interleukin-6(IL-6),interleukin^(-1)β(IL^(-1)β)and tumor necrosis factor-α(TNF-α),as well as cyclic adenosine monophosphate(cAMP),hypothalamic prostaglandin E_(2)(PGE_(2))and arginine vasopressin(AVP)in abdominal septum of hypothalamus were compared at the highest point of body temperature in each group.Results:After modeling,the increase of body temperature at 3 and 4 hours after modeling of high and medium doses of Qinghuo capsules groups was lower than that of the model group,and the increase of body temperature at 4 hours after modeling of low dose group was lower than that of the model group,and the difference had statistical significance(P<0.05).The levels of TNF-α,IL-6 and IL^(-1)βin the high dose group of Qinghuo capsules were lower than those in the model group,the levels of TNF-αand IL^(-1)βin the medium dose group were lower than those in the model group,and the level of TNF-αin the low dose group was lower than that in the model group,and the differences were statistically significant(P<0.05).The levels of cAMP and PGE2 in each dose group of Qinghuo capsules were lower than those in the model group,and the difference was statistically significant(P<0.05).There was no significant difference in the AVP level between the Qinghuo capsules groups and the model group(P>0.05).Conclusion:Qinghuo capsules can reduce the body temperature of fever rats with obvious antipyretic effect.Its antipyretic effect may be related to the reduction of various inflammatory factors and the inhibition of hypothalamic fever mediators PGE2 and cAMP.