基于STAT3-黑皮质素系统研究“数食甘美而多肥”的基本病机是痰瘀同病

The famous phrase“obesity is caused by frequent intake of rich and greasy foods”is the Chinese medicine for the common cause of metabolic disease , look for the basic pathogenesis will help to intervene the development of metabolic diseases.National Fund study shows that pre-natural, high-sugar Phlegm Method on rat obesity weight loss, lipid-lowering effect, transcriptome sequencing analysis revealed Phlegm law by activating STAT3-Melanocortin system.According to TCM theory and previous research,We hypothesize the basic pathogenesis of “obesity is caused by frequent intake of rich and greasy foods”is “coexistence of phlegm and blood-statsis”.STAT3-Melanocortin system to suppress appetite, regulate energy metabolism, and "obesity is caused by frequent intake of rich and greasy foods" leading to energy imbalance due to excessive intake are consistent.To the basic pathogenesis,this topic will use synchronic treating phlegm and blood stasis Dan-Gua Fang to disproof ,Hypothalamic neurons and High sugar plus digestive enzymes simulate "frequent intake of rich and greasy foods" will be the model, use STAT3-Melanocortin system as an entry point t, as this passage Phlegm law and regulation have metabolic effects, indicating that the basic pathogenesis of phlegm and blood with the disease. In vitro binding experiments for further analysis with the disease Phlegm phlegm, blood stasis severity and have relationships.This research is expected to reveal the basic pathogenesis of “obesity is caused by frequent intake of rich and greasy foods”,rich metabolic disease pathogenesis and for intervention to obesity Phlegm law as the core of metabolic syndrome evidence.

“数食甘美而多肥”是代谢性疾病的共同病因，寻找基本病机有助早期干预代谢性疾病发生发展。前期国家自然基金研究表明，痰瘀同治法对高糖饲料喂养型肥胖大鼠有减重、降糖、降脂作用，基因测序分析揭示痰瘀同治法能激活启动子STAT3。STAT3可启动黑皮质素系统。STAT3-黑皮质素系统能抑制食欲、调节代谢。据此推测“数食甘美而多肥”基本病机为痰瘀同病。本课题以痰瘀同治丹瓜方为治疗反证，以消化酶+高糖饲料模拟“数食甘美”肥胖模型鼠为研究对象，以STAT3-黑皮质素系统通路为切入点，如痰瘀同治法对此通路及其代谢效应有调控作用，表明基本病机为痰瘀同病。结合体外实验进一步分析痰瘀同病中痰、瘀的主次及先后关系。研究有望探明“数食甘美而多肥”的基本病机，丰富代谢性疾病中医病因病机的科学内涵，并为痰瘀同治法干预以肥胖为核心的代谢综合征提供证据。

以高糖、高热量、低纤维摄入的过多的饮食习惯为病因所引起的能量过剩，是随着现代社会发展日益突出的代谢性疾病的特点，并由此引起以肥胖为首先出现症状，以胰岛素抵抗为病理基础，出现高血糖、高血压、血脂紊乱为特征的代谢综合征，这与中医经典《黄帝内经》中所提到的“数食甘美而多肥”所相吻合，由此我们计划以中医理论为基础，探求“数食甘美而多肥”的基本病机，有望为干预代谢性疾病提供新思路、新方向。本研究从动物体内实验入手，以高糖加消化酶拟“数食甘美”大鼠模型，以丹瓜方为反证，观测糖耐量试验、糖化血红蛋白，血脂，检测STAT3-黑皮质素系统通路相关指标，揭示丹瓜方通过该通路的调控防治代谢病效果。另外，我们从体外细胞实验通过丹瓜方药液含药血清、活血药液含药血清、化痰药液含药血清干预下丘脑细胞，进一步证实痰瘀同治法调控STAT3-黑皮质素系统通路的作用。通过本研究证实了丹瓜方通过该通路的调控防治糖尿病效果，并通过反证法证实了“数食甘美而多肥”的基本病机为痰瘀互结，先痰后瘀。有望通过痰瘀同治法调控黑皮质素系统，防治由于数食甘美而多肥导致的代谢性疾病，为中医学代谢病研究提供新方向。