黄芪与不同剂量柴胡配伍的退热作用及机制的探讨

Study on Antipyretic Effects and Mechanism of Astragalus Complying with Different Dosages of Radix Bupleuri

目的:探讨黄芪与不同剂量柴胡配伍对脾虚发热大鼠模型的退热作用及机制。方法:雄性Wistar大鼠随机分为正常对照组、脾虚发热组、芪柴大、中、小剂量组、柴胡组共6组。采用饮食失节+游泳疲劳+LPS制备大鼠脾虚发热模型。实验第17d开始,各给药组大鼠分别按剂量4.56 g/kg、2.95 g/kg、2.41 g/kg、2.41 g/kg给予灌胃,正常组和脾虚发热组给予同体积蒸馏水,每日1次,连续6 d。第22天模型组和各给药组ip LPS(80μg/kg),正常对照组ip等量生理盐水。观测各组大鼠ip后不同时间点的体温,测定血中细胞因子和下丘脑体温调节递质的含量。结果:与正常组相比,脾虚发热组大鼠在ip LPS后各点体温均见不同程度升高,60 min和220 min时升高明显(P<0.05);血IL-2显著升高(P<0.05);下丘脑cAMP和PGE2显著升高(P<0.05),AVP呈下降趋势。与脾虚发热模型组相比,各给药组大鼠体温均出现不同程度下降(P<0.05),下丘脑PGE2或AVP呈现降低或升高趋势,其中柴胡组和芪柴小剂量组的体温下降明显,下丘脑IL-1β显著降低(P<0.05),芪柴大剂量组血IL-1β显著升高(P<0.05)。与芪柴大剂量组比,芪柴中、小剂量组及柴胡组血IL-1β均显著降低(P<0.05),芪柴中、小剂量组血IL-2显著升高(P<0.05)。结论:黄芪配伍柴胡不同剂量及单用大剂柴胡对脾虚发热模型均有不同程度的退热作用,其退热机制可能与降低中枢发热递质PGE2和升高AVP有关,黄芪与小剂柴胡配伍和单纯大剂柴胡的退热作用可能还涉及到中枢IL-1β的降低。

Objective： To explore the antipyretic action and mechanism of Astragalus complying with different dosages of Radix Bupleuri on the rat models of spleen-qi deficiency with fever. Methods： The male wistar rats were randomly assigned to the normal group,the spleen-qi deficiency with fever group,the astragalus with large dosage radix bupleuri group,the astragalus with medium dosage radix bupleuri group,the astragalus with small dosage radix bupleuri group,and the radix bupleuri group. The model rats of spleen-qi deficiency were prepared through excess fatigue and out of constant diet for 21 days. The medicine group rats were fed with 4. 56g / kg（ large）,2.95g / kg（ medium） 2. 41g / kg（ small） and 2. 41g / kg（ radix bupleuri only） once a day and the other two groups were given physiological saline from the seventeenth day. At 8： 00 am on the 22th day,the rats of model group and medicine groups were respectively intraperitonealy injected with lipopoly saccharide（ LPS,8 0 μg / kg） to induce fever. The rats of the normal group were given physiological saline.The rectal temperature was measured at different time after ip LPS. And then the amounts of cytokines in blood and transmitters which regulate temperature in hypothalamus were also measured. Results： Compared with the normal group,the temperature of rats in the spleen-qi deficiency with fever group raised to some extent at every observation time after ip LPS,especially at 60min and 220min（ P〈0. 05）. IL-2 in blood、CAMP and PGE2 in hypothalamus increased significantly（ P〈0. 05）. AVP in hypothalamus had decreased. Compared with the spleen-qi deficiency with fever group,the temperature of rats in every medicine group decreased significantly to some extent（ P〈0. 05）. CAMP and PGE2 in hypothalamus increased or decreased（ P〈0. 05）. The temperature declined and IL-1β in hypothalamus decreased significantly（ P〈0. 05） in the radix bupleuri group and the astragalus with small dosage radix bupleuri group. Blood of IL-1β increased significantly（ P〈0. 05） in the astragalus with large dosage radix bupleuri group. Compared with the astragalus with large dosage radix bupleuri group,blood IL-1β decreased significantly（ P〈0. 05） in the astragalus with medium and with small dosage radix bupleuri groups,as well as the radix bupleuri group. Blood IL-2 increased significantly（ P〈0. 05） in the astragalus with medium and with small dosage radix bupleuri groups. Conclusion： Astragalus complying with different dosage of radix bupleuri and only application of large dosage of radix bupleuri had antipyretic effect to the model rat of spleen-qi deficiency with fever. Its antipyretic mechanism may be connected with reducing central pyrexia amboceptor PGE2 and increasing AVP. And astragalus complying with small dosage of radix bupleuri and the only application of large dosage radix bupleuri may be also related to declining of central IL-1β.