目的 从代谢组学角度对姜炮制-配伍机制进行初步探索。方法 采用卵清白蛋白（OVA）+冰水浴法建立寒饮伏肺哮喘大鼠模型，随机分为对照组、模型组、苓甘五味（生/干/炮）姜辛汤组（SJF/GJF/PJF）及阳性药桂龙咳喘宁组（PC），给药后进行大鼠肺组织HE染色、肺泡灌洗液（BALF）炎性细胞计数，测定血清免疫球蛋白E（IgE）、白细胞介素-4（IL-4）、γ干扰素（IFN-γ）水平；同时采用GC-MS代谢组学技术进行非靶向代谢组学研究，寻找寒饮伏肺哮喘大鼠血清、尿液相关差异性代谢物，MetaboAnalyst构建相关代谢通路。结果 苓甘五味（生/干/炮）姜辛汤可改善大鼠肺组织病理变化，显著降低大鼠BALF炎性细胞计数及血清中IgE、IL-4水平，升高血清中IFN-γ水平；与对照组相比，寒饮伏肺哮喘大鼠体内共筛选出37种差异性代谢物（血清中15个、尿液中22个），MetaboAnalysis通路分析发现7条代谢通路可能与寒饮伏肺哮喘有关，涉及能量代谢、氧化应激等。苓甘五味（生/干/炮）姜辛汤干预后大鼠整体代谢轮廓趋向正常水平；且苓甘五味（干）姜辛汤治疗寒饮伏肺哮喘作用优于苓甘五味（生/炮）姜辛汤。结论 苓甘五味姜辛汤方中姜炮制成干姜入药治疗寒饮伏肺哮喘更为合理，其机制可能通过调节能量代谢、氧化应激等发挥作用。

Objective To investigate the effects of processing and compatibility of ginger for the treatment of cold asthma rats at the metabolomics level by gas chromatography-mass spectrometry (GC-MS). Methods The rats of cold asthma were established by ovalbumin (OVA) + ice water bath. The rats divided randomly into the control group, model group, Linggan Wuwei (fresh/dry/stir- frying) Jiangxin Decoction group and the positive drug Guilong Kechuanning group. The pathological changes of lung tissue were observed by HE staining; The inflammatory cell count in BALF and the content of IgE, IL-4 and IFN-γ in serum were determined. GC-MS was used to conduct the non-targeted metabolomics study to search the serum and urine related differential metabolites in rats with cold asthma, and MetaboAnalyst was used to construct related metabolic pathways. Results The results showed that Linggan Wuwei (fresh/dry/stir-frying) Jiangxin Decoction improved the pathological changes of rat lung tissue, significantly reduced the BALF inflammatory cell count in BALF and IgE and IL-4 levels in serum, and increased IFN-γ levels. Compared with the control group, 37 differential metabolites (15 in serum and 22 in urine) were screened in cold asthma rats. And seven metabolic pathways involving energy metabolism, oxidative stress may be associated with cold asthma by Metaboanalysis pathway analysis. The overall metabolic profile of the cold asthma rats with the intervention of Linggan Wuwei (fresh/dry/stir-frying) Jiangxin Decoction tended to normal levels. The effect of Linggan Wuwei (dry) Jiangxin Decoction on cold asthma was better than Linggan Wuwei (fresh/stir-frying) Jiangxin Decoction. Conclusion It is more reasonable to process ginger into dried ginger in Linggan Wuwei Jiangxin Decoction against cold asthma. Ginger processing-compatibility may play a therapeutic role in cold asthma rats by regulating energy metabolism and oxidative stress.

R285.5

安徽省自然科学基金项目（1708085MH196）；国家重点研发计划资助项目（RD19100084）