基于脂质组学从LRP6/Wnt信号通路研究隔药饼灸对高脂血症兔的调脂作用机制

Hyperlipidemia (hyperlipidemia, HLP) is an important risk factor of cardiovascular disease, herb-partition moxibustion is an effective treatment for HLP. Herb-partition moxibustion, as an integrative treatment for HLP combined with moxibustion, drugs and acupoints, could bring about multi-target, multi-channel systematic effect to regulate dyslipidemia; therefore, to reveal in-depth its mechanism is the inevitable trend of future research in this field. Lipidomics as a significant branch of metabonomics, has been an emerging research field in the latest years, which could disclose the mechanism of HLP from a systematic and overall perspective, and also provides a new pathway to elucidate the mechanism of lipid regulation of herb-partition moxibustion. It is said by newly reports that LRP6/Wnt signaling pathway plays an important role in the pathological process of HLP, and is considered to be a potential regulator of lipid metabolism. Based on lipidomics and LRP6/Wnt signaling pathway, using herb-partition moxibustion as an intervention to treat HLP rabbits, collecting samples of plasma and liver tissue, with the use of various biological technologies, including biochemical analyzer, trace protein electrophoresis, Western blotting, real-time quantitative polymerase chain reaction, as well as ultra performance liquid chromatography - biotechnology flight mass spectrometry, to elucidate the regulation of herb-partition moxibustion treatment for HLP rabbits on lipid markers, its metabolic pathways and metabolic networks, and also reveal the modulation mechanism of dyslipidemic metabolism of herb-partition moxibustion by LRP6/Wnt signaling pathway.

高脂血症（hyperlipidemia，HLP）是心脑血管疾病的重要危险因素，隔药饼灸是治疗HLP的有效针灸方案。隔药饼灸通过艾灸、药物、穴位，多靶点、多途径的系统整体调节而产生调脂效应，深入揭示其作用机理是未来研究的必然趋势。脂质组学从系统整体水平揭示HLP发生机制，是最近几年的研究热点，为隔药饼灸调脂作用机制研究提供了新的途径。新近研究表明，LRP6/Wnt信号通路在HLP形成的多个环节中发挥重要作用，被认为是潜在的脂质代谢调节剂。本课题拟基于脂质组学，以LRP6/Wnt信号通路为切入点，采用隔药饼灸，以HLP兔为受试对象，采集血浆和肝脏组织样品，运用蛋白质印迹、实时荧光定量聚合酶链反应、超高效液相色谱-飞行时间质谱联用等生物技术手段，揭示隔药饼灸对HLP兔的脂质标记物及其代谢途径与代谢网络的调节作用，揭示隔药饼灸通过LRP6/Wnt信号通路调脂的调控机制。

高脂血症（hyperlipidemia，HLP）是心脑血管疾病的重要危险因素，隔药饼灸是治疗HLP的有效针灸方案。隔药饼灸通过艾灸、药物、穴位，多靶点、多途径的系统整体调节而产生调脂效应，深入揭示其作用机理是未来研究的必然趋势。LRP6/Wnt信号通路在HLP形成的多个环节中发挥重要作用，被认为是潜在的脂质代谢调节剂。本课题以LRP6/Wnt信号通路为切入点，采用隔药饼灸，以HLP兔为受试对象，采集血浆和肝脏组织样品，运用全自动生化仪、蛋白质印迹、实时荧光定量聚合酶链反应等生物技术手段，揭示隔药饼灸通过LRP6/Wnt信号通路调脂的调控机制。研究表明隔药饼灸、悬灸及西药均能良性调节HLP模型兔的血脂水平，且隔药饼灸与西药疗效相当；隔药饼灸对高脂血症兔的血浆和肝脏脂质代谢的影响，初步揭示隔药饼灸可能通过调节高脂血症兔的磷脂类、鞘脂类、固醇酯类代谢而发挥调脂降脂的作用，为进一步深入分析隔药饼灸如何调整代谢通路与网络而调脂降脂奠定基础。HLP兔经过隔药饼灸治疗之后，隔药饼灸通过下调高脂血症兔的血清与肝组织中SP-1、血清与肝组织以及主动脉中IGF-1、心肌与肝组织中LRP6以及肝组织Wnt-1、β-catenin、SREBP-1c和HMGR的表达量，调节Wnt1--IGF1--SP1--SREBP信号通路，影响了Wnt信号通路的表达，发挥隔药饼灸的调脂降脂作用；HLP兔经隔药饼灸之后，肝脏组织中IGF-1的mRNA表达量降低，主动脉组织中IGF-1的mRNA含量降低，表明HLP兔经过隔药饼灸治疗之后，IGF1的含量发生了变化，而且可能与血脂的变化呈现负相关，推测可能IGF-1与高脂血症的血脂调节呈负性相关。