大青叶不同提取物解热作用比较及其机制研究

Study on Comparision of Antipyretic Effect of Different Folium Isatidis Extract and Its Mechanism

目的 比较大青叶正丁醇、乙酸乙酯和石油醚提取物对脂多糖所致大鼠发热模型的解热作用,初步探讨其作用机制。方法 72 只 SPF 级 SD 健康大鼠,按大鼠基础体温随机分为 6 组,即阴性对照组、模型组、阳性对照组、大青叶正丁醇提取物组、大青叶乙酸乙酯提取物组、大青叶石油醚提取物组,每组 12 只。连续给药 7 d,末次给药 30 min 后除阴性对照组外各组大鼠均给予 20 μg·kg^(–1)脂多糖溶液造模。观察各组大鼠在造模后 4 h 内的体温变化,同时比较大鼠体温最高点时各组血清白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、下丘脑前列腺素 E2(prostaglandin E2,PGE2)、环磷酸腺苷(cyclic adenosine monophosphate,c AMP)以及下丘脑腹中隔区精氨酸加压素(arginine vasopressin,AVP)水平。结果 大青叶正丁醇与乙酸乙酯提取物组在造模后 3,4 h 的体温升高幅度显著低于模型组(P<0.05 或 P<0.01)。大青叶正丁醇提取物组的 TNF-α、IL-6 水平显著低于模型组(P<0.01),大青叶乙酸乙酯提取物组的 TNF-α、IL-1β 水平显著低于模型组(P<0.05 或 P<0.01),大青叶石油醚提取物组的TNF-α 水平显著低于模型组(P<0.01)。大青叶正丁醇提取物组的 c AMP、AVP 水平显著低于模型组(P<0.01)。结论 大青叶正丁醇提取物和乙酸乙酯提取物具有一定的解热作用,其中正丁醇提取物解热效果最好,且各提取物均表现出较强的抗炎效果。大青叶正丁醇提取物的解热作用机制可能与降低 TNF-α、IL-6、IL-1β 水平、抑制下丘脑 c AMP 和降低腹中隔区中的 AVP 含量有关,而大青叶乙酸乙酯提取物的解热作用机制可能与降低 TNF-α、IL-1β 水平有关。

OBJECTIVE To comparative the antipyretic effect of n-butanol,ethyl acetate and petroleum ether extract of Folium Isatidis on lipopolysaccharide induced fever model in rats and to preliminarily discuss its mechanism.METHODS Seventy-two SPF SD healthy rats were randomly divided into 6 groups according to the basal body temperature of the rats,namely,negative control group,model group,positive control group,n-butanol extract group of Folium Isatis,ethyl acetate extract group of Folium Isatis,and petroleum ether extract group of Folium Isatis,with 12 rats in each group.After 7 d of continuous administration,30 min after the last administration rats in all groups except the negative control group were given 20μg·kg^(–1) lipopolysaccharide solution to model.The changes of body temperature within 4 h after model establishment were observed,and the serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),hypothalamic prostaglandin E2(PGE2),cyclic adenosine monophosphate(cAMP) and arginine vasopressin(AVP) in the abdominal septum of the hypothalamus were also compared at the highest point of body temperature in each group.RESULTS The increase of body temperature at 3 and 4 h after model establishment was significantly different from that of the model group(P<0.05 or P<0.01).The levels of TNF-α and IL-6 in the n-butanol extract group of Folium Isatidis were significantly lower than those in the model group(P<0.01),and the levels of TNF-α and IL-1β in the ethyl acetate extract group of Folium Isatidis were significantly lower than those in the model group(P<0.05 or P<0.01),and the levels of TNF-α in the petroleum ether extract group of Folium Isatidis were significantly lower than that in the model group(P<0.01).The levels of cAMP and AVP in the n-butanol extract group of Folium Isatidis were significantly lower than that in the model group(P<0.01).CONCLUSION The n-butanol extract and ethyl acetate extract of Folium Isatidis have a certain antipyretic effect,of which the n-butanol extract has the best effect,and each extract shows a strong anti-inflammatory effect.The antipyretic mechanism in the n-butanol extract of Folium Isatidis may be related to the decrease of TNF-α and IL-6 and IL-1β,and the inhibition of hypothalamic cAMP and the decrease of AVP content in ventral septal area,while the antipyretic mechanism in the ethyl acetate extract of Folium Isatidis may be related to the decrease of TNF-α and IL-1β.