基于转录组学的不同剂型藿香正气散对湿困脾胃大鼠的疗效及机制探讨

Effect and Mechanism of Different Formulations of Huoxiang Zhengqi Powder on Dampness Obstructing Spleen-Stomach Syndrome in Rats Based on Transcriptomics

目的:基于转录组学技术比较不同剂型藿香正气散对大鼠湿困脾胃证的疗效及潜在作用机制。方法:将SD大鼠随机分为6组:正常组,模型组,藿香正气滴丸高(5 g·kg^(-1))、低(1 g·kg^(-1))剂量组,藿香正气口服液高(10 mL·kg^(-1))、低(2 mL·kg^(-1))剂量组。采用综合物理造模方法建立湿困脾胃大鼠模型,共造模20 d,造模第11天灌胃给药。测量体质量、体长、尾长、腹围指数、自主活动次数以及结肠组织病理变化;运用转录组学技术检测结肠组织中差异基因表达情况。结果:与正常组比较,模型组大鼠体质量、体长、尾长、自主活动次数明显减少,腹围指数明显升高(P<0.05),结肠病理变化明显。藿香正气滴丸高、低剂量和藿香正气口服液高剂量能显著改善湿困脾胃大鼠宏观体征、行为学指标(P<0.05)和结肠病理学改变。但藿香正气口服液低剂量组对上述症状改善不显著(P>0.05)。转录组学测序分析结果显示,与正常组比较,湿困脾胃证模型组差异表达基因共525个;与模型组比较,藿香正气滴丸组差异表达基因共434个,藿香正气口服液组差异表达基因共255个。结论:两种剂型的藿香正气散均可改善大鼠湿困脾胃证,但藿香正气口服液低剂量时效果不明显。它们的共同作用机制与改善能量代谢、炎症反应以及调节免疫密切相关,而藿香正气滴丸可能还与氨基酸代谢有关。

Objective:The effect and potential mechanism of different formulations of Huoxiang Zhengqi Powder were compared in rats with dampness obstructing spleen-stomach syndrome(DOSSS)based on transcriptomics.Methods:Sprague Dawley(SD)rats were randomly divided into 6 groups:control group,model group,high-dose Huoxiang Zhengqi dropping pills group(5 g·kg^(-1)),low-dose Huoxiang Zhengqi dropping pills group(1 g·kg^(-1)),high-dose Huoxiang Zhengqi oral liquid group(10 mL·kg^(-1))and low-dose Huoxiang Zhengqi oral liquid group(2 mL·kg^(-1)).The rat model of DOSSS was established using a comprehensive physical modeling approach over a 20 day period,and the drugs were given by intragastric administration on the 11th day.Throughout the experiment,parameters including body mass,body and tail length,abdominal circumference index,spontaneous activity frequency,and pathological alterations in colon tissue were assessed.Transcriptomics was used to detect differentially expressed genes in colon tissues.Results:Compared with the control group,the body mass,body and tail length as well as the spontaneous activity frequency of the model group were significantly reduced,but the abdominal circumference index was significantly increased(P<0.05).Meanwhile,the model group showed obvious pathological changes.High and low doses Huoxiang Zhengqi dropping pills and high dose Huoxiang Zhengqi oral liquid administration could significantly improve the macroscopic signs,behavioral indexes(P<0.05)and colonic pathological changes of rats with DOSSS.However,the above-mentioned symptoms were not significantly improved in low-dose Huoxiang Zhengqi oral liquid group(P>0.05).Transcriptomic analysis showed that 525 differentially expressed genes were found in the DOSSS model group compared with the control group.Compared with the model group,434 and 255 differentially expressed genes were obtained in Huoxiang Zhengqi dropping pills group and Huoxiang Zhengqi oral liquid group,respectively.Conclusion:The two formulations of Huoxiang Zhengqi powder could both improve DOSSS in rats,but the effect of Huoxiang Zhengqi oral liquid was not obvious at low dose.Their joint mechanisms were closely related to improving energy metabolism,inflammatory response and immune regulation,and the mechanism of Huoxiang Zhengqi dropping pills might also be related to amino acid metabolism.