基于 GC-TOF/MS 代谢组学技术探讨藿香正气滴丸干预湿困脾胃型大鼠的作用机制

目的 通过基于气相色谱-飞行时间质谱联用 （GC-TOF/MS）技术的代谢组学方法探讨藿香正气滴丸干预湿困脾胃型大鼠的作用机制。方法 将雄性 SD 大鼠随机分为正常组、模型组和藿香正气滴丸组 （1 g·kg-1）。采用综合物理模型复制方法结合饮食失节制备湿困脾胃大鼠模型。灌胃给药，每日 1 次，连续给药 10 d。观察大鼠宏观体征和行为学指标 （体质量、体长、尾长、腹围指数与自主活动次数）。利用 GC-TOF/MS 方法对大鼠血清和尿液代谢组进行分析，鉴定与湿困脾胃相关的潜在生物标志物，分析藿香正气滴丸干预湿困脾胃型大鼠的代谢通路。结果 与正常组比较，模型组大鼠的体质量、体长、尾长、自主活动次数明显减少 （P＜0.05），腹围指数明显升高 （P＜0.05）。与模型组比较，藿香正气滴丸组大鼠的体质量、体长、自主活动次数明显增加（P＜0.05），腹围指数明显降低 （P＜0.05）。在大鼠血清、尿液中分别鉴定了 38、44 个与湿困脾胃相关的潜在生物标志物。藿香正气滴丸对模型大鼠的血清和尿液代谢表型能产生有效的干预，并能使血清、尿液中的17、13 个潜在生物标志物水平显著回调，共涉及 7 条代谢通路。结论 藿香正气滴丸对湿困脾胃型大鼠的干预机制可能与调节色氨酸代谢、组氨酸代谢、谷氨酸-谷氨酰胺代谢、能量代谢及肠道菌群等有关。

Exploration of the Mechanism of Huoxiang Zhengqi Dropping Pills Based on GC-TOF/MS Metabolo⁃mics Technology in Rats with Dampness Encumbering the Spleen and Stomach Type

Objective To explore the mechanism of Huoxiang Zhengqi Dropping Pills in treating dampness encumbering the spleen and stomach type rats by metabolomics method based on gas chromatography-time of flight mass spectrometry（GC-TOF/MS）. Methods Male SD rats were randomly divided into normal group，model group and Huoxiang Zhengqi Dropping Pills group （1 g·kg-1）. The rat model of dampness encumbering the spleen and stomach was prepared by comprehensive physical modeling method combined with improper diet. Intragastric administration was performed once a day for 10 consecutive days. The macroscopic signs and behavioral indexes（body mass，body length，tail length，abdominal circumference index and spontaneous activities frequency） of rats were observed. GC-TOF/MS method was used to analyze the serum and urine metabolome of rats，identify potential biomarkers related to dampness encumbering the spleen and stomach，and analyze the metabolic pathway of Huoxiang Zhengqi Dropping Pills in rats with dampness encumbering the spleen and stomach. Results Compared with the normal group,the body mass,body length,tail length and spontaneous activities frequency of the rats in the model group were significantly reduced （P＜0.05），and the abdominal circumference index was significantly increased （P＜0.05）. Compared with the model group，the body mass，body length and spontaneous activities frequency of the rats in the Huoxiang Zhengqi Dropping Pills group were significantly increased（P＜0.05），and the abdominal circumference index was significantly decreased （P＜0.05）. A total of 38 and 44 potential biomarkers related to dampness encumbering the spleen and stomach were identified in rat serum and urine，respectively. Huoxiang Zhengqi Dropping Pills can effectively interfere with the serum and urine metabolic phenotypes of model rats， and can significantly reverse 17 and 13 potential biomarkers in serum and urine，involving a total of 7 metabolic pathways. Conclusion The intervention mechanism of Huoxiang Zhengqi Dropping Pills on rats with dampness encumbering the spleen and stomach syndrome may be related to the regulation of tryptophan metabolism，histidine metabolism，glutamate-glutamine metabolism，energy metabolism and intestinal flora.