基于脂质组学研究归芪益母散对能量负平衡奶牛产后脂肪动员的调节机制

The postpartum physiological stress caused by negative energy balance（NEB） in early lactation is mainly compensated by body fat mobilization in dairy cows. Lipid metabolism disorder, immunosuppression and oxidative stress resulting from the excessive mobilization can induce many postpartum diseases. Studies have shown that the preventive and therapeutic effects of Gui Qi Yimu Powder on postpartum diseases in dairy cows are related to its immuno-enhancing and antioxidant activities. Our team has also found that the prescription can regulate lipid metabolism in postpartum dairy cows, but its mechanism is not clear. In this project, the regulation effect of Gui Qi Yimu powder on postpartum body fat mobilization will be first analysed by the changes in lipid metabolism hormones and nonesterified fatty acids in NEB dairy cows; Then the influences of the prescription on lipid metabolic profiles of blood, milk and liver tissue in different postpartum stages in NEB dairy cows will be investigated using lipidomics; The biomarkers and metabolic pathways in response to Gui Qi Yimu Powder will be selected through construction of lipid mobilization networks to reveal the regulation mechanism of the prescription on postpartum lipid mobilization in dairy cows. The results can provide a further theoretical basis for the application of the prescription to postpartum health care in dairy cow, and also provide new ideas for the development of other traditional Chinese medicine compounds for postpartum health care in dairy cows.

奶牛产后通过体脂动员以弥补泌乳早期能量负平衡造成的生理应激状态，但过度动员引起的脂质代谢紊乱、免疫抑制和氧化应激会诱发产后诸多疾病。以往研究表明归芪益母散对奶牛产后疾病的防治作用仅与其免疫增强和抗氧化作用有关。课题组前期研究发现该方还有调节奶牛产后脂质代谢的作用，但其机制尚不清楚。本项目通过脂质代谢激素和非酯化脂肪酸等指标的变化，分析归芪益母散对能量负平衡奶牛产后体脂动员的调节作用；采用脂质组学方法研究该方对能量负平衡奶牛产后不同阶段血液、乳汁和肝组织脂类代谢轮廓的影响；通过脂肪动员网络的构建筛选响应归芪益母散的生物标志物及代谢通路，揭示该方对能量负平衡奶牛产后脂肪动员的调节机制。研究结果为该方在奶牛产后保健中的应用提供更深层次的理论依据，也为研发其它奶牛产后保健中药复方提供新的思路。

奶牛产后通过体脂动员以弥补泌乳早期能量负平衡造成的生理应激状态，但过度动员引起的脂质代谢紊乱、免疫抑制和氧化应激会诱发产后诸多疾病。本项目旨在揭示归芪益母散对能量负平衡奶牛产后脂肪动员的调节机制。项目研究了奶牛产后血液生化指标和炎性因子变化规律及归芪益母散的调节作用，结果提示奶牛围产后期由于能量负平衡脂肪代谢与肝功能发生了明显变动和炎性反应，而归芪益母散具有较好的缓解作用；采用UPLC-MS/MS代谢组学技术研究归芪益母散对产后奶牛瘤胃代谢物和短链脂肪酸的调节作用，结果提示奶牛受分娩影响，产后7天内瘤胃代谢机能发生了较大波动，归芪益母散通过调节产后奶牛瘤胃菌群增强瘤胃代谢机能和发酵功能；项目研究了奶牛产后血液代谢组变化规律及归芪益母散的调节作用，结果提示奶牛产后处于代谢和氧化应激状态，归芪益母散可通过调节甘油磷脂代谢、皮质醇代谢、色氨酸代谢、精氨酸和脯氨酸代谢改善代谢应激和氧化应激；项目采用脂质组学研究了归芪益母散对产后奶牛脂质代谢的调节作用，研究结果显示归芪益母散对花生四烯酸代谢、TRP通道的炎症介质调、PPAR信号通路、醛固酮的合成和分泌、血管平滑肌收缩、血清素能突触通路有明显影响；项目首次采用氧化三甲胺（TMAO）建立了奶牛脂肪肝细胞模型，研究了归芪益母散对奶牛脂肪肝细胞脂肪蓄积的调节作用，结果显示不同剂量归芪益母散均能减缓奶牛肝细胞脂肪蓄积，荧光定量PCR结果进一步揭示该方减缓奶牛肝细胞脂肪蓄积的机制与其能调节脂氧化关键基因PPARa及其下游靶基因CPT2和脂合成基因ChREBP的表达有关。研究结果为归芪益母散在奶牛产后保健中的应用提供深层次的理论依据，也为研发其它奶牛产后保健中药复方提供新的思路。