基于GC-MS代谢组学技术的狭叶柴胡解热作用研究

目的 采用GC-MS代谢组学技术研究狭叶柴胡的解热作用,并初步探讨其作用机制.方法 SD大鼠随机分为对照组,模型组,狭叶柴胡提取物高、中、低剂量(生药40、20、10 g/kg)组、阿司匹林(100 mg/kg)阳性对照组,干酵母诱导SD大鼠发热后分2次给药.造模后5～10 h每隔1h观察大鼠的体温变化；采集造模后10 h大鼠血浆,进行GC-MS代谢组学分析,并寻找发热的潜在生物标志物.结果 阿司匹林具有很好的解热效果,在给药2h后体温即与对照组无显著差异(P＞0.05).不同剂量的狭叶柴胡提取物使发热大鼠的体温有不同程度的降低,解热作用与剂量相关；高剂量组起效较快,在第1次给药后1h即与模型组有显著差异(P＜0.01)；中剂量组在第2次给药后1h效果最好,体温与对照组相比无显著差异(P＞0.05)；低剂量组大鼠体温在各个时间点与模型组相比均无显著差异,体温曲线波动较大,表明药物在该剂量虽可干预体温的升高,但未产生明显效果.通过代谢组学技术指认了与发热相关的17个潜在生物标志物,且不同剂量狭叶柴胡提取物均能调节这些标志物的改变.结论 狭叶柴胡具有良好的解热作用且与剂量相关,其可能从酶抑制、神经递质、糖脂代谢、氨基酸及能量代谢等多层面协同发挥作用,具有多靶点性.

Antipyretic effect of Bupleurum scorzonerifolium based on GC-MS metabonomics

Objective To evaluate the antipyretic effect of Bupleurum scorzonerifolium based on GC-MS metabolomics and explore its mechanism. Methods Rats were randomly divided into control, model, high-, mid-, low-dose B. scorzonerifolium extract (40, 20, and 10 g/kg), and Aspirin (100 mg/kg) positive control groups. The fever rats induced by yeast were administered twice. The body temperature changes of rats were observed at the 5th, 6th, 7th, 8th, 9th, and 10th hours after modeling; Meanwhile, plasma samples were collected at the 10th hour and subjected to GC-MS analysis to find potential biomarkers of fever. Results Aspirin showed antipyretic effect well. The temperature showed no significant difference compared with the control group 2 h after administration (P > 0.05). Different doses of extract from B. scorzonerifolium showed the antipyretic effect at varying degrees, which presented the obvious dose-dependent antipyretic effect. The high-dose group had a faster onset, and there was a significant difference (P < 0.01) 1 h after the first administration compared with the model group. The mid-dose group achieved the best antipyretic effect 1 h after the second administration, and there was no significant difference compared with the normal group (P > 0.05). Compared with the model group, low-dose group showed no significant differences at each time point. The body temperature showed a large fluctuation, indicating the drugs could interfere with the increase of body temperature but did not reach a significant antipyretic effect. Seventeen potential biomarkers were identified from the loading plot based on the metabolomics and the different doses of B. scorzonerifolium extract could regulate the biomarkers. Conclusion B. scorzonerifolium has the significant antipyretic effect in a dose-dependent manner and the antipyretic role may be related to the synergism of enzyme inhibition, neurotransmitter, glucose and lipid metabolism, amino acid metabolism, energy metabolism with the multi-targets.