桂附地黄丸调控阳虚体质能量代谢及神经－内分泌网络的肠道微生态学作用机制

Yang deficiency constitution is a common biased constitution, it’s closely related with the bronchial asthma, chronic obstructive pulmonary disease. It is with the feature of cold intolerance and it directly affects the quality of life. Previous studies have found that Gui Fu Di Huang pills can ameliorate the cold intolerance of people with Yang deficiency constitution, which mechanism may relate to the regulation of energy metabolism and nervous - endocrine network. Recent studies have shown that the interaction between the Chinese herbs and the intestinal flora plays an important role in the treatment. It is presumed that Gui Fu Di Huang Pills adjust the energy metabolism and nervous - endocrine network of the Yang deficiency constitution people by regulating certain metabolic pathways of the intestinal flora. 16SrDNA gene sequencing method is adopted to observe the intestinal flora characteristics at different time points of the Yang deficiency constitution people taking Gui Fu Di Huang Pills. The study is to illustrate the changes of the energy metabolism and nervous - endocrine network at different time points from the macro and micro perspectives, and seek the common trends of the intestinal flora variation and nervous - endocrine network changes. The application of metagenomics correlation analysis can further reveal the characteristics of the functional intestinal flora and the regulation pathways of the energy metabolism and nerve – endocrine network. This study will enable the understanding of the mechanism of Chinese patent medicine in regulating the energy metabolism of the Yang deficiency constitution people and provide scientific proof for developing TCM probiotics targeting on intestinal flora, and to further enhance the quality of life of Yang deficiency constitution people, lay the foundation of prevention and treatment of related diseases.

阳虚体质是一种常见的偏颇体质，与支气管哮喘、慢性阻塞性肺病等疾病的发生发展密切相关。不耐寒冷是其标志性特征，直接影响健康相关生命质量。前期研究发现，桂附地黄丸调理阳虚体质的作用机制可能与调节能量代谢及神经-内分泌网络有关。现代研究表明，中药与肠道菌群的互作效应在中药治疗中起到重要作用。据此我们提出“桂附地黄丸通过调控功能肠道菌群作用于特定代谢通路，改善阳虚体质能量代谢及神经-内分泌网络紊乱状态”的假说。拟采用16S rDNA序列分析法，在桂附地黄丸调理阳虚体质的不同时点，观察肠道菌群结构与能量代谢及神经-内分泌网络的共变化趋势；应用宏基因组学关联分析进一步揭示特征功能菌群及其调控能量代谢、神经-内分泌网络的作用通路。本项目将有助于理解中药调体的肠道微生态学作用机制，为研发以肠道菌群为靶点的中药微生态制剂提供科学依据，进一步为提升阳虚体质人群生命质量、防治相关疾病奠定基础。

阳虚体质是一种常见的偏颇体质，与支气管哮喘、慢性阻塞性肺病等疾病的发生发展密切相关。不耐寒冷是其标志性特征，直接影响健康相关生命质量。本项目拟从肠道菌群入手，研究桂附地黄丸改善阳虚体质能量代谢及神经-内分泌网络紊乱状态的机制。.本项目采用16SrDNA序列分析法，在桂附地黄丸调理阳虚体质的不同时点，观察肠道菌群结构与能量代谢及神经-内分泌网络的共变化趋势；应用宏基因组学关联分析进一步揭示特征功能菌群及其调控能量代谢、神经-内分泌网络的作用通路。肠道菌群的研究初步发现桂附地黄丸可增加阳虚体质肠道菌群多样性及丰度，肠道菌群结构在第8周变化最显著，与血糖、甘油三酯、低密度脂蛋白呈现共变化趋势的菌群为毛螺菌科（Lachnospiraceae）、梭菌科（Clostridiaceae）、韦荣球菌科（Veillonellaceae）、克里斯滕森菌科（Christensenellaceae）等。瘤胃菌科（Ruminococcaceae）、毛螺菌科（Lachnospiraceae）在桂附地黄丸调理阳虚体质的过程中发挥了关键作用，特征菌群功能富集在碳水化合物转运和代谢、能量生成和转换等功能类别中，涉及能量代谢相关通路；临床研究发现桂附地黄丸改善阳虚体质效果优于单纯生活方式干预，起效快、效果持久，桂附地黄丸可能是通过提高促肾上腺皮质激素释放激素和血清皮质醇达到改善阳虚体质的目的，同时采用改良德尔菲法初步构建包含主观指标9项，客观指标3项的阳虚体质干预效果评价指标体系。.本项目通过动态观察桂附地黄丸调体过程中肠道菌群与宿主代谢的共变化趋势，初步明确中药调理阳虚体质的靶向菌群，为研发以肠道菌群为靶点的调体中药微生态制剂提供科学依据；在一定程度上解释了桂附地黄丸调理阳虚体质能量代谢、神经-内分泌网络的肠道菌群作用机制，为改善体质状态、防治相关疾病提供指导；通过建立阳虚体质干预效果评价指标体系，为调体干预评估提供参考。