藿香正气口服液对湿困脾胃证大鼠尿液代谢组学的影响

Urinary Metabonomics Study on Effect of Huoxiang Zhengqi Oral Liquid in Rats with Dampness Obstructing Spleen-Stomach Syndrome

目的从代谢网路层面阐明大鼠湿困脾胃证本质及藿香正气口服液的治疗效果。方法采用综合物理造模方法造成湿困脾胃证大鼠。观察大鼠脏器系数变化和结肠组织病理改变,采用酶联免疫吸附(ELISA)法检测大鼠血清免疫球蛋白G(IgG)水平,并利用核磁共振氢谱(~1H-NMR)技术建立大鼠尿液的代谢物谱图,分析藿香正气口服液治疗湿困脾胃证大鼠后相关潜在生物标志物的变化。结果与对照组比较,湿困脾胃证大鼠(模型组)脾脏、胸腺系数及血清IgG水平显著降低(P<0.05),尿液代谢物组发生显著改变(P<0.05)。与模型组比较,藿香正气口服液能提高湿困脾胃证大鼠胸腺、脾脏系数及IgG水平,差异有统计学意义(P<0.05)。藿香正气口服液能对湿困脾胃证大鼠尿液代谢紊乱产生有效的干预,并对尿液中与湿困脾胃证相关的5个潜在生物标志物产生显著的回调,与模型组比较差异有统计学意义(P<0.05)。结论藿香正气口服液治疗大鼠湿困脾胃证的机制可能与调节IgG水平以及机体三羧酸循环、肠道菌群改变有关。

Objective To explore the essence of dampness obstructing spleen-stomach syndrome （DOSS） in rats and the effect of Huoxiang Zhengqi Oral Liquid（HZOL） on DOSS. Methods Comprehensive physical methods were applied to establish the rat DOSS model. Indexes of spleen and thymus, the pathological change of colon, as well as the serum level of IgG in rats were assessed. Moreover, a proton nuclear magnetic resonance （1H-NMR） based metabonomies approach was developed to profile DOSS-related metabolic perturbations in rat urine and to investigate the intervention effect of HZOL in rats. Results Compared with the healthy control group, rats with DOSS showed lower indexes of spleen and thymus, decreased level of IgG in serum, together with metabolic perturbations in urine （P 〈 0.05）. The disturbed metabolic state associated with DOSS in rat urine could be restored by HZOL. Meanwhile, five potential biomarkers related to DOSS in rat urine were reversed by administration of HZOL （P 〈 0.05 ）. Conclusion The current study demonstrated that HZOL exerted protective effect against DOSS in rats, which was probably mediated by regulation of IgG level and restoration of tricarboxyhc acid cycle （TCA） and gut microbiota disturbance.