连翘酯苷A对酵母致热小鼠体温及TRPA1的影响

Effect of Forsythiaside A on Temperature and Expression of TRPA1 in Mice with Yeast Induced Pyrexia

目的：通过观察连翘酯苷A（forsythiaside A,FA）对酵母致热小鼠体温的影响以及体温调节中枢及外周温度敏感瞬时感受器电位离子通道（transient receptor potential,TRP）A1表达影响,明确FA的解热作用及可能的机制。方法：60只雄性C57BL/6小鼠随机平均分为以下6组,分别为正常组,模型组,FA不同剂量组（2,4,8 mg·kg^-1）和阳性药阿司匹林组（90mg·kg^-1）。除正常组外,其他5组小鼠以背部皮下注射酵母混悬液法建立发热模型,并于造模前以及造模后17~22 h检测小鼠体温情况;造模后22 h处死小鼠,取下丘脑和背根神经节（dorsal root ganglion,DRG）,通过免疫组化和Western blot方法检测TRPA1的表达水平。结果：与正常组比较,注射酵母后模型组小鼠体温明显上升,17 h达到高峰期（P〈0.01）,下丘脑和背根神经节中TRPA1水平显著降低（P〈0.01）;与模型组比较,FA剂量4,8 mg·kg^-1可显著降低酵母引起的小鼠体温升高,上调下丘脑体温调节主要神经核团下丘脑室旁核（PVN）和视上核（SO）,以及外周DRG中TRPA1水平（P〈0.05,P〈0.01）。结论：FA能降低酵母致热小鼠的体温,其作用可能与其对下丘脑和DRG中TRPA1的有效调节有关。

Objective： To investigate the effect of forsythiaside A（ FA） on body temperature,heatregulating center and temperature-sensitive transient receptor potential（ TRP） A1 expression of mice with yeast induced fever,so as to elucidate the mechanism of the antipyretic effect and potential mechanism of FA. Method：Sixty male C57 BL /6 mice were randomly divided into six groups： normal group,model group,different dosages（ 2,4,8 mg·kg^-1） of FA-treated group,aspirin group（ as the positive control,90 mg·kg^-1）,with 10 mice in each group. The pyrexia model was induced by injection of yeast suspension subcutaneously. Rectal temperature was recorded before and 17-22 h after pyrexia induction. At the 22 h after injection of yeast,the mice were sacrificed to collect their hypothalamus and dorsal root ganglion（ DRG）. The expression of TRPA1 was detected by immunohistochemistry and Western blot. Result： Compared with the normal group,the rectal temperature of the mice in the model group notably increased after injection of yeast,reaching the peak at 17 h（ P〈0. 01）. In the meanwhile,the TRPA1 level in hypothalamus and DRG of the model group significantly reduced. Compared with the model group,FA（ 4,8 mg·kg^-1） group showed significant decrease in the elevated temperature of mice induced by yeast,and up-regulation in the expression of TRPA1 in paraventricular nuclei（ PVN）,supraoptic nucleus（ SO） and DRG（ P〈0. 05,P〈0. 01）. Conclusion： FA can reduce the temperature of fevered mice induced by yeast,which may be related to their effective regulation of TRPA1 in hypothalamus and DRG.